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Biomedical subjects

B Korbmacher

Publications and source records attributed to B Korbmacher.

At least 19 recordsLinked to original sources

Does adenosine pharmacologically precondition human myocardium during coronary bypass surgery?

AIM: Adenosine (Ado) triggers ischemic preconditioning. We investigated whether Ado provides additional myocardial protection in patients during intermittent aortic cross-clamping (IAC) bypass surgery. METHODS: The placebo group was made of 15 male of 66+/-8 years while the Ado group was made of 19 male of 65+/-10 years. The patients of the Ado group had a 3-vessel heart disease and were treated with elective surgery. With the aortic cross-clamping, Ado or vehicle were infused over 10 min at systemic pressure together with sufficient blood via the aortic root. Blood samples before anaesthesia and onset of ECC, 1 hour after end of surgery, and on day 1 and 2 post-surgery to assess CK-MB and troponin I were performed. Hemodynamic measures (heart rate, left ventricular pressure, max/min pressure rise, central venous pressure) before installation and 15 min after completion of the coronary artery bypass. Different ECGs for electrophysiological analyses were performed. RESULTS: Hemodynamic and laboratory measures revealed no significant advantages of either protocol. Mortality rate was zero in both groups. CONCLUSIONS: The comparable outcome is likely due to cardioprotection provided by both IAC bypass surgery and hypothermia, which might obscure beneficial effects of pharmacological preconditioning in patients with good left ventricular function (ejection fraction >50%). As the benefit might have been marginal, it may well become apparent in a larger study on patients with more severe left ventricular dysfunction.

Adenosine↗

Determination of the coronary flow reserve of the LAD in patients with HOCM using the intracoronary Doppler catheter.

OBJECTIVE: Hypertrophic obstructive cardiomyopathy (HOCM) is still a serious problem that is characterized by an increasing hypertrophy of the cardiac muscle. The aim of this study was to investigate the hypothesis whether in HOCM the coronary flow reserve in the left anterior descending artery (LAD) is influenced by pharmacologic stimulation or stimulation using a pacemaker. PATIENTS AND METHODS: The study was carried out in 15 patients (6 male, 9 female) with the typical echocardiographic signs of HOCM without coronary artery disease. Using an intracoronary Doppler catheter the average peak velocity and the absolute coronary flow reserve were determined in the proximal, medial and distal part of the LAD under influence of Papaverine, Substance P and under pacemaker stimulation. The coronary square plane was calculated angiographically under the influence of Substance P. Moreover, the retrograde flow was studied and the coherence between the increase of the coronary square plane and the coronary flow reserve were investigated. For statistical analysis the mean value, the standard error of the mean, Spearman's correlation coefficient and the t-test were calculated. RESULTS: Under pharmacologic stimulation higher values in the average peak velocity were observed compared to pacemaker stimulation. A retrograde flow was observed in 8 out of 10 patients. The coronary flow reserve was higher under pharmacologic influence than under pacemaker stimulation. A coherence between the increase of the coronary square plane and the coronary flow reserve was not found. CONCLUSIONS: So far, from the published data concerning the characteristics of coronary flow in HOCM patients, only the retrograde flow was reproducible in our patient group. However, a decrease of the coronary flow reserve compared to a healthy control group of the literature could not be observed. Nevertheless ischemia in the subordinate vessels and on the base of microcirculation cannot be excluded.

Aged↗

Intermittent aortic cross-clamping for coronary artery bypass grafting: a review of a safe, fast, simple, and successful technique.

Since the very beginning of coronary artery bypass grafting, the search for optimal myocardial protection has fascinated both clinicians and basic researchers. This retrospective review of a large patient cohort aims to display the advantages of one of the protective procedures, namely simple, intermittent aortic cross-clamping (IAC). Thus, this review aims to significantly contribute to daily bypass surgery. This review reports on coronary patients who were all operated on in international centers using IAC such that this review presents the state of the art on IAC. In addition, this review reports on the usage of IAC for more than 2 decades in the clinic of Dr. Bircks, Duesseldorf (DE) and the clinics of his former students. A meta-analysis of published data of international centers summarizes 7 837 operated patients with a total mortality of 123 (=1.6%). This excellent outcome compares well to the results of the Bircks'-related centers, where between 1978 and 2001, a total of 41 573 patients were revascularized with the help of IAC according to the original protocol. The total mortality was 778 (1.9%), with the lowest mortality rate (1.2%) in the largest center (Bad Oeynhausen, DE). According to the presented experience, IAC for coronary revascularization proves to be a highly effective method for myocardial protection; it has convincingly proven to be simple, safe and cost-efficient.

Aorta↗

Repair of critical aortic coarctation in neonatal age.

BACKGROUND: The data of 111 (male: 64; female: 47) in the period of 1967 until 12/93 consecutive operated neonatals (<1 month) were studied retrospectively (mean weight 3270 g, mean age at operation 14 days). METHODS: Preductal anatomy was present in 96 patients. The coarctation was isolated in 30 patients (group I), 34 patients had additional large ventricular septal defects (group II) and 47 had complex heart disease (group III). The preoperative heart catheterization revealed a gradient of <20 mmHg in 35%, >20 mmHg in 51.4% and >50 mmHg in 12.9%. The indication for repair was conservatively untreatable heart insufficiency. In the vast majority (n=97) of patients resection and end-to-end anastomosis were performed, in 31 cases using an absorbable suture, in 18 of these using a continuous suture line. In 4 patients a subclavian flap angioplasty (SFA) was done, in 4 a patch enlargement, 4 times a repair was described as not possible and in 2 patients there was no gradient after division of the ductus. RESULTS: Early lethality was 3.3% (n=1) in group I, 24.2% (n=8) died in group II and 39.1% (n=18) in group III; after introducing Prostaglandin E1 0% in group I, 15% in II and 25% in III. Relevant recoarctation (Gradient >20 mmHg) developed in 9 (among them 4 with hypoplastic arch, 2 after SFA) of the 77 long-term survivors; 6 of these were reoperated on, 5 without residual gradient, 1 with a gradient of 25 mmHg without clinical symptoms (after 4 years). In the last 3 patients a balloon dilation was carried out without residual gradient. Mean follow-up time was 6 (0-24) years. No patient needs antihypertensive treatment. The cumulative survival rate is 96.7% (+6.6%) for group I, 77.4% (+15.0%) for II and 51.9% (+16.6%) for III. CONCLUSIONS: Resection and end-to-end anastomosis using a continuous absorbable suture is the method of choice at theoretical considerations and in our experiences. The number of recoarctations in neonatal age is relatively high; reinterventions (operation respectively dilation) can be done safely and successfully.

Age Factors↗

Perioperative levels of atrial natriuretic peptide and troponin-T in patients with uncomplicated coronary artery surgery.

BACKGROUND HYPOTHESIS: increased ANP levels after uncomplicated coronary artery surgery (CAS) indicate functional reduction. METHODS EXPERIMENTAL DESIGN: prospective, randomized. Preoperative upto the 12 week postoperative. SETTING: Thoracic and Cardiovascular Surgery, University of Düsseldorf. PATIENTS: 15 patients (mean age: 58+/-6.1 years; 13 months, 2 weeks; no myocardial infarction, no congestive heart failure) with 3 vessel disease. INTERVENTIONS: levels of atrial natriuretic peptide (ANP) (pg/ml; radioimmunoassay), Troponin T (TnT) (ng/ml; ELISA test), haemodynamic parameters, ECG monitoring, m-mode echocardiography (Echo). MEASURES: increase of ANP, TnT levels during extracorporeal circulation (ECC), decrease after operation. RESULTS: Maximal increase of ANP from preoperative 90+/-10 (M+/-SEM) pg/ml (p<0.05) up to intraoperative 380+/-38 pg/ml. Ten days postoperative ANP (26+/-33 pg/ml) still threefold increased compared to preoperative level. Increasement of TnT from preoperative 0.02+/-0.01 ng/ml upto intraoperative 3.44+/-0.47 ng/ml. Ten days postoperative TnT concentration normal (0.13+/-0.11 ng/ml). Correlation of ANP and TnT five min after bypass up to 6 hrs postoperative (p<0.05, r =3.4). Increase of left atrial diameter preoperative 42.2+/-1.1 mm up to 46.8+/-1.2 mm (p<0.05) 10 days postoperative. LVEDD, EF changed from preoperative 51.1+/-0.9 mm, 73+/-2% to 54.5+/-1.2 mm, 65+/-4% 10 days postoperative. CONCLUSIONS: Threefold increase of ANP 10 days postoperative and return of TnT levels to normal under consideration of datas of echo show, that ANP is suitable to indicate the meanterm, functional, myocardial reduction. Increased ANP levels, atrial dilatation and dysfunction are important signs of cardial functional reduction after CAS.

Adult↗

Left ventricular dysfunction and disturbed O(2)-utilization in stunned myocardium: influence of ischemic preconditioning.

OBJECTIVE: Myocardial dysfunction during postischemic reperfusion is frequently reported only in terms of left ventricular (LV) systolic properties. We additionally assessed diastolic properties, the cardiovascular tone and in particular, the relation between ventricular function and myocardial oxygen consumption. Moreover, these measures are investigated after cardioprotection via ischemic preconditioning (IP). However, this phenomenon is not fully understood, and therefore cardioprotective methods like ischemic preconditioning might provide only insufficient protection. METHODS: In a total of 17 isolated rabbit hearts, perfused with an erythrocyte suspension (Hct 30%), we investigated the effect of 20 min low-flow ischemia also on diastolic properties, coronary resistance and cardiac energetics (n=9). During control and 30 min after the onset of reperfusion, LV systolic function was assessed in terms of aortic flow, dP/dt(max) and the end-systolic pressure-volume relation (ESPVR). Early relaxation was evaluated via dP/dt(min) and diastolic properties were assessed via the end-diastolic pressure-volume relation (EDPVR), i.e. using the equation LVP(ed)=c.exp(m.LVV(ed)), where c equals the LVP(ed)-axis intercept and m equals LV stiffness. In addition, coronary resistance (R(cor)) and the pressure-volume area (PVA) were calculated. Total oxygen consumption (MVO(2)) was calculated as well as the contractile efficiency (E = inverse slope of the MVO(2)-PVA relation). In a second series (n=8) the effect of ischemic preconditioning (3 min no-flow and 8 min reperfusion before the 20 min low-flow ischemia) was tested. RESULTS: In the first series, systolic function was impaired during reperfusion: aortic flow to 32% of control, dP/dt(max) to 74% and the slope of ESPVR to 73%. Early relaxation in terms of dP/dt(min) decreased to 76%. The slope of the EDPVR was steeper in stunned myocardium with an increase of the ventricular stiffness (m increased from 3.2 to 4.1) and with an upward shift of the EDPVR (c from 0.6 to 2.4 mmHg). Coronary resistance was increased (from 0.9 to 1.4 mmHg/ml per min) and PVA was significantly decreased to 68%, whereas MVO(2) was not, indicating also a decrease in contractile efficiency E from 28 to 14%. In the second series, recovery of systolic function was significantly improved by IP compared with the first series (aortic flow 56% of preischemic control, dP/dt(max) to 91% and ESPVR to 78%). LV stiffness m was also slightly increased from 3.1 to 3.9 and again, c was elevated, indicating no beneficial effect for diastolic properties including dP/dt(min) (77%). But IP improved R(cor) significantly (from 0.9 to only 1.0 mmHg/ml per min) and efficiency E to 21% (from 27% during control). CONCLUSION: Brief episodes of ischemia not only induce systolic but also diastolic and vascular stunning at almost maintained MVO(2). The decreased contractile efficiency clearly indicates an impaired O(2)-utilization of the contractile apparatus. Ischemic preconditioning did not improve diastolic function during reperfusion, but it provided protection with respect to vascular stunning and myocardial energetics.

Animals↗

In vitro determination of cardiac ventricular volumes using MRI at 1.0 T in a porcine heart model.

PURPOSE: To determine the accuracy of a 1.0 T MR system with a standard gradient system for quantification of left and right ventricular volumes. A porcine heart model in vitro was used. METHODS: In eight explanted porcine hearts the atria were removed and the aorta and the pulmonary truncus were cannulated. Defined volumes were injected into the ventricles. Magnetic resonance imaging (MRI): FFE-EPI (Multishot EPI) was used. Papillary muscles and trabeculae were excluded. True volumes and MR measurements were analysed separately for both ventricles and by both investigators. RESULTS: The correlation of the true volumes and MR measurements was >0.99. MRI was found to be investigator independent in assessing right and left ventricular volumes in vitro. CONCLUSIONS: MRI at 1.0 T using standard equipment can be used to quantitate cardiac ventricular volumes in vitro with high accuracy.

Animals↗

Long-term results after repair of total anomalous pulmonary venous connection.

BACKGROUND: Operative strategies and early results concerning repair of Total Anomalous Pulmonary Venous Connection (TAPVC) are relatively well known. Less well defined data are available to evaluate the long-term outcome. We would therefore like to contribute our long-term data in this presentation. PATIENTS AND METHODS: Between 1958 and 1992 52 consecutive patients aged two days to 42 years (15 neonates, 16 infants, 9 children and 12 adults) with TAPVC were operated on. The data were collected retrospectively from the records. In 24 patients, a current follow-up study was performed, including clinical evaluation, echocardiography, and a twenty-four-hour ambulatory ECG. RESULTS: Early mortality was 34.6% (n = 18). The postoperative follow-up period ranged from 4 months to 28 years (mean 10.7 years). There were 4 late deaths, yielding an overall long-term mortality of 7.7% (4/52). Causes of death were severe hypoplasia of central pulmonary veins in 1, ventricular fibrillation (2) and non-cardiac in one case. 80% of the operative survivors were available for assessment. Preoperatively, 11 of these patients were in NYHA functional class II, six in class III and seven in class IV. After treatment, 22 patients were in class I and two in class II. Ventricular function was evaluated by echocardiography and invasive catheterization. Only two of 24 patients (8%) showed an abnormal IVS-motion and enlargement of the right ventricle. Cardiac catheterization revealed a mean PA pressure of 26 mmHg, the peak systolic pressure in the RV was 34 mmHg. All 24 long-term survivors underwent assessment of cardiac rhythm by 24 h electrocardiogramm (ECG) monitoring. Significant arrhythmias were recorded in 11 of 24 cases (46%), including sinus node dysfunction in 3 patients. Multiform ventricular ectopic beats were evaluated in 9 cases. According to the Lown classification, 7 patients were class I while 2 cases were considered to be class IV. CONCLUSIONS: A normal hemodynamic state can be achieved in most cases. Significant arrhythmias may exist in asymptomatic patients late after surgical correction of TAPVC, and therefore, long-term follow-up of these patients, including 24 h ECG monitoring, is recommended, even if they are asymptomatic.

Adolescent↗

Right and left ventricular volume measurements in an animal heart model in vitro: first experiences with cardiac MRI at 1.0 T.

The aim of this study was to determine the accuracy in quantifying right and left ventricular volumes using a 1.0-T system and commercially available, standard equipment. For exact comparison of MRI measurements and real volumes we used an animal heart model ex vivo. Eight pig hearts were explanted and prepared by removal of the atria. Aorta and pulmonary truncus were cannulated. Definable volumes were injected into the ventricles. Magnetic resonance imaging was performed at 1.0 T (Gyroscan T10 NT, Philips, Eindhoven, The Netherlands); sequence: fast field echo-echo planar (multishot EPI); body coil; MR software: Cardiac Application Package (Philips). Statistical analysis correlated the real volumes and MR measurements separately for both ventricles and two investigators (SAS, ANOVA). For both ventricles and both investigators the correlation between real volumes and MR measurements was greater than 0.99. There was no significant systematic false estimation for both ventricles. Magnetic resonance imaging at 1.0 T using standard hardware and software equipment enables the quantification of right and left ventricular volumes with high approximation to the real volumes in vitro. There is a clear restriction in translating these data into a clinical application because under experimental conditions no motion-induced artifacts existed.

Animals↗

[Atrial natriuretic peptide as an indicator of mild postoperative cardiac dysfunction after uncomplicated bypass surgery].

Plasma levels of ANP (pg/ml; radioimmunoassay) as a parameter for postischemic dysfunction and levels of Troponin T (TnT) (ng/ml; ELISA test) as a parameter for postischemic cellular damage were determined in 15 patients with coronary artery disease (CAD) (mean age: 58 +/- 6.1 years; 13 m, 2 w; with no history of myocardial infarction and no signs for congestive heart failure) prior to, during and after extracorporal circulation (ECC). Under standardized conditions during the ECC basic parameters concerning the cardial hemodynamic (heart rate (HR); systolic (RRsys, mmHg), diastolic pressure (RR dia, mmHg) central venous pressure (CVP, mmHg); left atrial pressure (LAP, mmHg); left ventricular enddiastolic pressure (LVEDP, mmHg)) and ECG monitoring blood samples were performed: 1) prior to operation (op); 2) prior to CPB; 3) 1 h CPB; 4) 5 min after CPB; 5) 1 h after CPB; 6) 6 h postoperative (postop); 7) 24 h postop; 8) 48 h postop; 9) 10 days postop. Also the left atrial diameter (LAD, mm) and the left ventricular enddiastolic diameter at Q (LVEDD, mm) pre- and postop were documented with m-mode echocardiography (Echo) and ejection fraction (EF, %) was calculated. The bypass operations were performed with intermittent aortic cross-clamping with open venae cavae (CVP: 0-5 mmHg) and moderate hypothermia. For the determination of ANP levels and TnT levels in arterial and venous blood, a double-antibody (AB) radioimmunoassay and an ELISA test were used. Concerning the patients with CAD there was a maximal increase of ANP from preoperative 90 +/- 10 (M +/- SEM) pg/ml (p < 0.05) up to intraoperative 380 +/- 38 pg/ml. Ten days postop, the ANP level was with 262 +/- 33 pg/ml still increased threefold in comparison to the preoperative level. TnT showed an increase from preoperative 0.02 +/- 0.01 ng/ml up to intraoperative 3.44 +/- 0.47 ng/ml. Ten days postop the TnT concentration was at the preoperative level with 0.13 +/- 0.11 ng/ml. Five minutes after bypass up to 48 h postop, ANP and TnT levels were correlated (p < 0.05, r = 3.4). There was an increase of the LAD from preoperative 42.2 +/- 1.1 mm up to 46.8 +/- 1.2 mm (p < 0.05) 10 days postop as determined by m-mode echo. LVEDD and EF changed from preoperative 51.1 +/- 0.9 mm and 73 +/- 2% to 54.5 +/- 1.2 mm and 65 +/- 4% 10 days postop. The significant increase of TnT (172-fold) indicates the cellular, myocardial injury, caused by the operation without signs in ECG recordings and no signs of congestive heart failure. The significantly increased ANP level up to the 10th day postop indicate sa very sensitive prolonged, postischemic dysfunction, which is not compensated 10 days postop.

Adult↗

Myocardial efficiency in stunned myocardium. Comparison of Ca(2+)-sensitization and PDE III-inhibition on energy consumption.

OBJECTIVE: In stunned myocardium oxygen consumption is relatively high compared with the reduced ventricular function. On the other hand, inotropic stimulation is frequently required to improve postischemic ventricular dysfunction. However, inotropic agents which act via intracellular increased calcium result in a higher oxygen demand. Therefore Ca(2+)-sensitization might be a favorable alternative. METHODS: The effects of a novel Ca(2+)-sensitizer (EMD 60263, 10 microM, group 1) were compared with a phosphodiesterase (PDE) III-inhibitor (enoximon, 20 microM, group 2) on 14 isolated, blood-perfused rabbit hearts during reperfusion after a global ischemia of 20 min. Ventricular function, the pressure-volume area (PVA, a measure of total mechanical work), and total myocardial oxygen consumption (MVO(2)) were assessed. Contractile efficiency (EF(cont)), derived from the reciprocal of the slope of the MVO(2)-PVA relation, and external efficiency (EF(ex), stroke work/MVO(2)), were calculated. RESULTS: At matched heart rate (group 1: 141+/-10 min(-1) group 2: 151+/-28 min(-1)) and end-diastolic volume (1.3+/-0.2 ml) systolic variables were significantly decreased in stunned myocardium: LVP(max) to 57+/-13% of control value in group 1 and to 76+/-7% in group 2, aortic flow to 20+/-4 vs. 25+/-8%. PVA was decreased to 57+/-13 and 67+/-11%, MVO(2) was non-significantly decreased to 73+/-22 and 88+/-14%. After administration of either inotropic agent LVP(max) was significantly improved to 96+/-12 vs. 90+/-8% compared with preischemic levels, aortic flow to 103+/-24 vs. 88+/-9%, and PVA 99+/-11 vs. 89+/-16%, respectively. EMD 60263 increased MVO(2) to control levels (107+/-9%), and enoximon raised MVO(2) even more significantly above control (139+/-13%). Both myocardial efficiency indices were significantly diminished during reperfusion: EF(ex) to 14+/-9 vs. 23+/-7% and EF(cont) to 71+/-7 vs. 65+/-9% compared with preischemic levels. EF(ex) (109+/-21%) was significantly, but EF(cont) only slightly (84+/-11%) increased after administration of EMD 60263, whereas EF(ex) (57+/-13%) and EF(cont) (71+/-12%) remained depressed after enoximon. CONCLUSIONS: In stunned myocardium, the decreased efficiency indices show that energy utilization is disturbed. Both agents recruited an inotropic reserve, whereas Ca(2+)-sensitization seemed to be more favorable in terms of myocardial efficiency indices. These results indicate that alteration of myocardial calcium sensitivity contributes a major part to postischemic dysfunction. Therefore, Ca(2+)-sensitization may potentially be a superior method for inotropic support in the postischemic heart.

Animals↗

Change of sternal perfusion following preparation of the internal thoracic artery--a scintigraphical study.

BACKGROUND: Today the internal thoracic artery (ITA) is the bypass graft of choice due to its superior long-term patency rate. It was the aim of this present prospective study to investigate possible perfusion disturbances and consecutive impaired wound healing induced by the ITA preparation. The sternal perfusion was assessed by bone scintigraphy. METHODS: Forty-four patients were included in the study. There were three groups: group I (control, no ITA preparation; n = 12); group II (preparation of the left ITA; n = 21); group III (preparation of both ITAs; n = 11). In all patients a median sternotomy was performed. A bone scintigraphy was performed 4 days before and 12 days after the bypass procedure. Scintigraphical pictures of all patients were assessed visually (one specialized investigator) and the impulse rate was counted by the aid of a computer program. RESULTS: Results of both evaluation methods showed congruently that neither the use of the left nor of both ITAs causes a statistically significant impairment of sternal perfusion. The percentage of postoperative increase of the rate of impulses was in group I: total sternum 55%; right side 56%; left side 55%. The respective numbers for group II were 58, 63 and 53%, and for group III 54, 52 and 56%. Surprisingly, perfusion scans in group II revealed an increase in the right sternal half after left ITA preparation. This may be due to the additional blood flow demand of collaterals branching between the right ITA and contralateral intercostal arteries representing a compensatory mechanism of the loss of the left ITA. During the observed postoperative time frame (mean 15 days) no healing disturbance of the sternal wound occurred in any patient. CONCLUSION: According to the present data the use of one or both ITAs does not cause an increase of healing disturbances, consecutive to a postoperatively decreased sternal blood perfusion.

Adult↗

Does ischemic preconditioning require reperfusion before index ischemia?

BACKGROUND: Ischemic preconditioning (IP) is initiated through one or several short bouts of ischemia and reperfusion which precede a prolonged ischemia. To test whether a reperfusion must precede the prolonged index ischemia, a series without reperfusion (intraischemic preconditioning: IIP) and a series with gradual onset of ischemia, i.e. ramp ischemia (RI), which is possibly related to the development of hibernation, was compared to conventional IP (CIP). METHOD: Experiments were performed an 27 blood-perfused rabbit hearts (Langendorff apparatus) that were randomized into one of four series: (1) control (n = 7): 60 min normal flow - 60 min low flow (10%) ischemia - 60 min reperfusion. (2) CIP (n = 7): 4 times 5 min zero flow with 10 min reperfusion each - 60 min low flow (10%) - ischemia 60 min reperfusion. (3) IIP (n = 7): 50 min normal flow - 10 min no flow - 60min low flow (10%) ischemia -4 60min reperfusion. (4) RI (n=6): gradual reduction to 10% flow during 60min - 60min low flow (10%) ischemia - 60min reperfusion. At the end of each protocol, the infarcted area was assessed. RESULTS: The infarct area in control hearts was 6.7+/-1.4% (means+/-SEM) of LV total area, in CIP hearts 2.6+/-0.8%, in IIP hearts 3.1+/-0.5%, and in RI hearts 3.0+/-0.3% (all p<0.05 vs. control). The differences between the three protection protocols were statistically not significant, and no protective protocol reduced post-ischemic myocardial dysfunction. CONCLUSION: The preconditioning effect (infarct size reduction) appears not to depend on intermittent reperfusion. Thus, the protective mechanism of IP develops during the initial ischemia that precedes the index ischemia. Alternatively, low-flow ischemia is effectively a sort of reperfusion.

Animals↗

Volumetric analysis of the right and left ventricle in a porcine heart model: comparison of three-dimensional echocardiography, magnetic resonance imaging and angiocardiography.

UNLABELLED: Three-dimensional echocardiography and magnetic resonance imaging allow the volumetric analysis of ventricular volumes independent of geometric assumptions. The aim of the study was to compare these methods and the common angiocardiography in a cardiac model of known volume. METHODS/MATERIALS: Right and left ventricular (RV, LV-) volumes were measured in a specific animal model directly ('true volume') and with different imaging techniques. Three-dimensional echocardiography (3D-Echo) and magnetic resonance imaging (MRI), both of which permit a volume estimation without necessitating geometric assumptions, and angiocardiographic volumetry which is based on the Simpson rule were used in this study. RESULTS: The best results were achieved with MRI (RV: r(2)=0.99, mean difference: -1. 9+/-3.3%; LV: difference r(2)=0.99,: 2.9+/-5.0%). Likewise, 3D-Echo showed a very good correlation with the true volumes (RV: r(2)=0.93, difference: 9.3+/-6.3%; LV r(2)=0.96, difference: 4.8+/-9.9%). The greatest deviations were observed during angiocardiographic volumetry (LV: r(2)=0.98; difference: 14.4+/-9.2%), particularly when measuring the right ventricle (RV: r(2)=0.82, difference: 57. 9+/-40.1%). Consequently, the direct comparison between 3D-Echo and the other methods yielded the best correspondence with MRI (RV: Bias: 3.7 ml, limits of agreement: 7.7 ml; LV: Bias: 3.7 ml, limits of agreement: 4.9 ml). In contrast, the differences between 3D-Echo and angiocardiography were marked (RV: Bias: 25.5 ml, limits of agreement: 11.1 ml; LV: Bias: 8.7 ml, limits of agreement: 13.2 ml). CONCLUSION: In a porcine cardiac model, 3D-Echo permits a relatively precise measurement of ventricular volumes with a slight under-estimation. MRI yielded the most precise volumetry, and the correlation between 3D-Echo and MRI was quite good. Particularly for the right ventricle, the angiocardiographic measurement was attached with the greatest error and thus appears ill-suited for the volumetry of geometrically more complex ventricles.

Analysis of Variance↗

Basal metabolism does not account for high O2 consumption in stunned myocardium.

Myocardial O2 consumption (MVo2) in stunned myocardium is relatively high compared with the reduced ventricular function. The mechanism of this "oxygen paradox" could occur at different levels: basal metabolism, excitation-contraction coupling, and energy production. In one previously reported series on 12 isolated, blood-perfused rabbit hearts, left ventricular systolic and diastolic function in stunned myocardium were significantly decreased compared with control, whereas total MVo2 was not. The MVo2 for the unloaded contraction was overproportionately high for the decreased function in stunned myocardium, and contractile efficiency was clearly deteriorated. To assess whether the basal metabolism specifically is elevated in stunned myocardium, a second series (n = 14) with a similar protocol was performed in this study. Basal MVo2 after KCl arrest (0.5 +/- 0.3 ml.min-1.100 g-1) was significantly lower than that measured after KCl arrest (1.2 +/- 0.5 ml.min-1.100 g-1) in an additional series on nonischemic hearts (n = 8). Our conclusion is that basal MVo2 in stunned myocardium is not elevated. Thus this O2-consuming portion of total MVo2 is not responsible for the inefficiency in stunned myocardium. Instead, a "metabolic stunning" occurs at the level of both excitation-contraction coupling and force development by the contractile apparatus.

Animals↗

Different responses of non-ischemic and post-ischemic myocardium towards Ca2+ sensitization.

We tested whether decreased Ca2+ sensitivity is a major cause for dysfunctional stunned myocardium. The experiments employed a novel Ca2+ sensitizing agent: the thiadiazinone derivative EMD 60 263. Experiments were done on 14 isolated, blood-perfused rabbit hearts. After control, seven hearts were subjected to 20 min no-flow ischemia, and then allowed to recover during 30 min reperfusion. Thereafter, EMD 60 263 was administered (3, 10 and 30 microm). For comparison, the effect of the same doses was investigated in seven non-ischemic hearts. At the low dose, the agent improved ventricular systolic function in the post-ischemic group significantly (LVPmax: 65+/-13 v 91+/-17 mmHg; dP/dtmax: 845+/-235 v 1300+/-350 mmHg/s), and non-significantly in the non-ischemic group (LVPmax: 115+/-35 v 132+/-39 mmHg; dP/dtmax: 1415+/-545 v 1885+/-720 mmHg/s). Early relaxation (dP/dtmin) was slightly improved in both groups (800+/-225 v 1050+/-220 mmHg/s post-ischemic; 1120+/-315 v 1205+/-285 mmHg/s non-ischemic). Heart rate was increased (151+/-35 v 175+/-45 beats/min) in the post-ischemic group and was unaffected in the non-ischemic group. At the higher dose, systolic ventricular function in the post-ischemic group was further improved (LVPmax: 109+/-17 mmHg, dP/dtmax: 1330+/-180 mmHg/s), but tended to decrease in the non-ischemic group (LVPmax: 121+/-40 mmHg, dP/dtmax: 1605+/-680 mmHg/s). This dose decreased heart rate in both groups (133+/-34 and 134+/-23 beats/min). 30 microm EMD 60 263 had deleterious effects in both groups. The different responses towards Ca2+ sensitization suggest that a decrease in Ca2+ sensitivity might play a role in dysfunctional stunned myocardium. Therefore, Ca2+ sensitizing agents of the thiadiazinone type could be useful to recruit a positive inotropic reserve in stunned myocardium.

Action Potentials↗

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

OBJECTIVE: To amplify the description of myocardial stunning. DESIGN: Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS: 15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES: Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS: Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS: Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus.

Animals↗