Biomedical subjects

J D Schipke

Publications and source records attributed to J D Schipke.

At least 19 recordsLinked to original sources

PubMed2001

[Gregg phenomenon and garden hose effect].

Under physiologic circumstances, cardiac function determines myocardial oxygen consumption and consequently coronary perfusion. Surprisingly, in a reverse direction, improved coronary perfusion also increased myocardial oxygen consumption and contractile function. This experimental finding, now 40 years old, is termed the Gregg phenomenon. Some 10 years later, in experiments by Arnold and co-workers, an isolated increase in perfusion pressure improved ventricular function. In this context, the term 'gardenhose effect' was coined, implying a hydraulic explanation of the Gregg phenomenon. In the following, we attempt to distinguish the Gregg phenomenon from the gardenhose effect and to critically evaluate them.

Animals↗

PubMed2001

Another view of myocardial hibernation.

This manuscript brings together three newer concepts: myocardial hibernation, heterogeneity in myocardial blood flow and oxidative metabolism, and effects of hibernating animal serum on non-hibernators. Myocardial hibernation is viewed as a protective mechanism that helps to maintain myocardial integrity and viability by down-regulating contractile function as an adaptation to reduced blood flow. Myocardial flow is considerably heterogeneous. Consequently, oxygen supply to the myocardium is also heterogeneous. Many lines of evidence show a close correlation between regional flow and regional metabolism. In low-flow/low-metabolism areas, myocardial function must be reduced, since the myocardium would otherwise undergo necrosis. Because no regional histological differences exist, the pattern of heterogeneity seems to shift over time. Hence, we hypothesize that such very regional hibernation presents an evolutionary, protective mechanism, permitting subsequent myocardial areas to rest within the ceaselessly working heart. We also hypothesize that a similar mechanism ensures the down-regulation of function following myocardial ischemia in order to induce myocardial hibernation on a broader level. Surprisingly, a substance (opioid in nature) contained in hibernator serum both induced hibernation-like state in non-hibernators and suppressed myocardial oxygen consumption. Thus, we lastly hypothesize that myocardial hibernation is a remnant of the early stages of evolution and is closer to physiological hibernation than traditionally viewed.

Animals↗

PubMed2001

Effect of immersion, submersion, and scuba diving on heart rate variability.

BACKGROUND: Heart rate variability (HRV) describes the cyclic variations in heart rate and offers a non-invasive tool for investigating the modulatory effects of neural mechanisms elicited by the autonomic nervous system on intrinsic heart rate. OBJECTIVE: To introduce the HRV concept to healthy volunteers under control conditions and during scuba diving. In contrast with more established manoeuvres, diving probably activates both the sympathetic and parasympathetic nervous system through various stimuli-for example, through cardiac stretch receptors, respiration pattern, psychological stress, and diving reflex. A further aim of the study was to introduce a measure for determining a candidate's ability to scuba dive by providing (a) standard values for HRV measures (three from the time domain and three from the frequency domain) and (b) physiological responses to a strenuous manoeuvre such as scuba diving. METHODS: Twenty five trained scuba divers were investigated while diving under pool conditions (27 degrees C) after the effects of head out immersion and submersion on HRV had been studied. RESULTS AND CONCLUSIONS: (a) Immersion under pool conditions is a powerful stimulus for both the sympathetic and parasympathetic nervous system. (b) As neither the heart rate nor the HRV changed on going from immersion to submersion, the parasympathetic activation was probably due to haemodynamic alterations. (c) All HRV measures showed an increase in the parasympathetic activity. (d) If a physiological HRV is a mechanism for providing adaptability and flexibility, diving should not provoke circulatory problems in healthy subjects. (e) Either a lower than normal HRV under control conditions or a reduction in HRV induced by diving would be unphysiological, and a scuba diving candidate showing such characteristics should be further investigated.

Adult↗

PubMed2000

Optimal method to achieve consistently low defibrillation energy requirements.

Reduction of the defibrillation energy requirement offers the opportunity to decrease implantable cardioverter defibrillator (ICD) size and to increase device longevity. Therefore, the purpose of this prospective study was to obtain confirmed defibrillation thresholds (DFTs) of < or = 15 J in each patient with an endocardial dual-coil lead system incorporating an active pectoral pulse generator (TRIAD lead system: RV- --> SVC+ + CAN+). According to our previous clinical and experimental studies, we tried to lower DFTs that were > 15 J by repositioning the distal coil of the endocardial lead system in the right ventricle. A total of 190 consecutive patients requiring ICDs for ventricular fibrillation and/or recurrent ventricular tachycardia were investigated at the time of ICD implantation (42 women, 148 men; mean age 61.9 +/- 12.0 years; mean left ventricular ejection fraction 42.7 +/- 16.6%). Coronary artery disease was present in 139 patients; nonischemic dilated cardiomyopathy in 34 patients; and other etiologies in 17 patients; 47 patients had undergone previous cardiac surgery. Regardless of optimal pacing and sensing parameters, for patients having DFTs > 15, we repositioned the distal coil of the endocardial lead system toward the intraventricular septum to include this part of both ventricles within the electrical defibrillating field. In 177 of 190 patients, induced ventricular fibrillation was successfully terminated with < or = 15 J (group I) using the initial lead position. Repositioning of the endocardial lead was necessary in 13 patients whose DFT(plus) (DFT(plus) = second additional success at lowest energy level) were > 15 J (group II). In all patients, repositioning was successful within a 15 J energy level (100% success). The mean DFT(plus) was 7.3 +/- 3.5 J (group I) and 11.0 +/- 4.5 J (group II; p<0.005). The mean DFT(plus) of all patients enrolled in the study was 7.6 +/- 3.7 J (range: 2 to 15 J). In 87% of all patients, DFT(plus) of < or = 10 J was achieved. Repositioning of the endocardial lead in the right ventricle is a simple and effective method to reduce intraoperative high DFTs. As a result of this procedure, ICDs with a 20 J output should be sufficient for the vast majority (87%) of our patients. Furthermore, we were able to avoid additional subcutaneous or epicardial electrodes in all patients.

Aged↗

PubMed2000

[Myocardial hibernation: another view].

In the following, three newer concepts are brought together: myocardial hibernation, heterogeneity in myocardial blood flow and oxidative metabolism, and effects of hibernating animal serum on non-hibernators. Myocardial hibernation is viewed as a protective mechanism that helps to maintain myocardial integrity and viability by down-regulating contractile function as an adaptation to reduced blood flow. Myocardial flow is considerably heterogeneous. Consequently, oxygen supply to the myocardium is also heterogeneous. Many lines of evidence show a close correlation between regional flow and regional metabolism. In low-flow/low-metabolism areas, myocardial function must be reduced, since the myocardium would otherwise undergo necrosis. Thus, others and we hypothesize that function must be down-regulated to induce hibernation in low-flow areas. Because no regional histologic differences exist (the mitochondria are uniformly distributed within the myocardium), the pattern of heterogeneity seems to shift over time. Hence, we hypothesize that such very regional hibernation presents an evolutionary, protective mechanism, permitting subsequent myocardial areas to rest within the ceaselessly working heart. We also hypothesize that this mechanism ensures the down-regulation of function following myocardial ischemia in order to induce myocardial hibernation on a broader level. Surprisingly, a substance (opioid in nature) contained in hibernator serum both induced hibernation-like state in non-hibernators and suppressed myocardial oxygen consumption. Thus, we lastly hypothesize that myocardial hibernation is a remnant of the early stages of evolution and is closer to physiologic hibernation than traditionally viewed.

Animals↗

PubMed2000

Potential role of endothelin-1 and endothelin antagonists in cardiovascular diseases.

The endothelins comprise a family of three isopeptides ET-1, ET-2 and ET-3, whereby ET-1 appears to be the most relevant in humans. They act in a paracrine manner on ETA and ETB receptors. ET-1 plays an important role in the cardiovascular system. In addition, it modulates vasomotion and growth processes, and it participates in thrombogenesis and neutrophil adhesion. This review summarizes some of the current literature pertaining to the physiological and pathophysiological significance of ET-1, focusing the assets and drawbacks of elevated ET-1 levels. In this regard, modulation of the endothelin system by either receptor blockade or by inhibition of endothelin converting enzyme is expected to provide novel therapeutic drug strategies.

Animals↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

Heterogeneity of local myocardial flow and oxidative metabolism.

In mammalian hearts, local myocardial flow (LMF) varies between 20 and 200% of the mean. It is not clear whether oxidative metabolism has a similar degree of heterogeneity. Therefore, we investigated the relation between LMF and local oxidative metabolism in isolated rabbit hearts. Buffer oxygenation with (18)O(2) resulted in labeled myocardial oxidation water (H(2)(18)O). In four hearts, myocardial oxygen consumption (MVO(2)) was calculated from the H(2)(18)O production and compared with that calculated according to Fick. In eight additional hearts, LMF was measured using microspheres. Coronary venous H(2)(18)O kinetics and local H(2)(18)O residues were determined and analyzed by mathematical modeling. MVO(2) recovery from H(2)(18)O was >93% compared with that according to Fick. LMF ranged from 1.91 to 11.24 ml. min(-1). g(-1), and local H(2)(18)O residue ranged from 0.41 to 1.04 micromol/g. Both variables correlated (r = 0.62, n = 64, P < 0.001). Measurements in nine hearts were fitted by modeling using capillary permeability-surface area products (PS(c)) from 2 to 10 ml. min(-1). g(-1). With flow-proportional PS(c), a 3.33-fold difference in LMF was associated with a 6.45-fold difference in local MVO(2). Both LMF and local oxidative metabolism are spatially heterogeneous, and they correlate to one another.

Animals↗

PubMed1998

Effect of implantable cardioverter/defibrillator lead placement in the right ventricle on defibrillation energy requirements. A combined experimental and clinical study.

OBJECTIVES: The effect of implantable cardioverter/defibrillator (ICD) lead placement in the right ventricle (RV) on defibrillation efficacy has not been thoroughly investigated. Therefore, the goal of this combined experimental and clinical study was to evaluate the effect of a septal and a non-septal position of the right ventricular endocardial spring lead on defibrillation energy. METHODS: In 12 isoflurane-anaesthetized swine and subsequently in 8 patients who underwent ICD implantation, two different positions of the distal spring lead in the RV were investigated in randomized order: non-septal position (free wall of the RV) and septal position (interventricular septum). For each position, separate 50% probability determinations of energy (E50), peak voltage (V50) and peak current (A50) were calculated using the three reversal up/down defibrillation procedure. The E50, V50, A50 and impedance (I) were averaged and compared using the two-sided t-test for paired samples. RESULTS: Both the experimental study and the clinical study demonstrated that placing the distal defibrillation lead near to the septum rather than near to the ventricular free wall resulted both in the swine and in the patients in significantly lower E50-31.6%/ - 37.1%, V50-16.1%/-20.9% and A50 -10.0%/ - 24.2%, respectively. Defibrillation impedances were significantly reduced only in the experimental study. CONCLUSIONS: Defibrillation efficacy depends on the position of the distal spring electrode in the RV. A septal position significantly reduces the energy requirements compared to a non-septal position. The decrease in energy requirements might be explained by an increase in current flow through the septum and the posterolateral wall of the left ventricle. reserved

Animals↗

PubMed1998

Pharmacologic heart rate reduction: effect of a novel, specific bradycardic agent on the heart.

Because heart rate (HR) is a major determinant of myocardial oxygen consumption (MVO2) a decrease in HR could prevent ischemia or reduce its consequences. We examined the effects of a novel bradycardic agent of the benzazepinone type, DK-AH 269 (DK), on ventricular function and perfusion in 12 isolated, blood-perfused rabbit hearts. HR was significantly reduced by 1mumol/L DK (160 +/- 28 vs. 124 +/- 23 min-1); diastole lengthened from 235 +/- 69 to 334 +/- 85 ms. Aortic flow tended to fall after DK (50.0 +/- 29.6 vs. 35.6 +/- 21.5 ml/min), but stroke volume remained unchanged (0.29 +/- 0.16 vs. 0.28 +/- 0.17 ml) following DK. Peak left-ventricular pressure (LVPmax) (106 +/- 29 vs. 92 +/- 35 mmHg) and dp/dtmax (1482 +/- 582 vs. 1247 +/- 644 mmHg/s) were decreased. dp/dtmin, as a measure of early relaxation, was also decreased (-1361 +/- 362 vs, -1125 +/- 488 mmHg/s), whereas the end-diastolic pressure (LVPed) was increased (20 +/- 12 vs. 25 +/- 17 mmHg). Coronary blood flow (CBF) per beat was not affected by DK: 0.07 +/- 0.02 vs. 0.07 +/- 0.02 ml. However, the coronary resistance increased with DK from 0.76 +/- 0.29 to 1.13 +/- 0.66 mmHg/(ml/min/100 g). The MVO2 was decreased (6.8 +/- 3.4 vs. 5.9 +/- 2.8 ml/min/100 g). The relation between subendocardial and subepicardial flow (colored microspheres) was unchanged after DK (1.12 +/- 0.22 vs. 1.13 +/- 0.16). Using electrical pacing to restore the control HR, dp/dtmax, LVPed, and MVO2 were nearly restored to predrug levels. In contrast, stroke volume, LVPmax, dp/dtmin and CBF per beat were less than control. In summary: DK effectively reduces heart rate and increases diastole. In parallel with the moderately reduced contractile function, MVO2 is reduced whereas CBF per beat is preserved. These results suggest that this novel bradycardic agent could be useful in treating unwanted tachycardia in the experimental setting, postoperative tachycardia in patients with heart disease or be useful even in treating coronary heart disease.

Animals↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1996

Cardiac efficiency during coronary occlusion and during reperfusion after emergency revascularization under cardioprotection.

Myocardial infarction in consequence of a coronary artery occlusion presents a serious problem. It is the aim of any emergency revascularization to minimize the ischemia-induced damage or to salvage reversibly injured myocardium. In experiments on 8 anesthetized pigs, myocardial protection by orthograde perfusion with a high-volume cardioplegic solution was studied under controlled conditions. The left anterior descending artery (LAD) was occluded for 60 min. Then cardiopulmonary bypass was instituted and cardioplegia induced by 8 min perfusion of Bretschneider HTK solution into the aortic root. After 15 min global ischemia, the LAD was "revascularized' and 150 min reperfusion followed. Except for the early relaxation (dP/dtmin) and mean thickening velocity in the ischemic myocardium, all variables remained essentially unchanged during LAD occlusion. During the entire reperfusion, heart rate was significantly increased compared to control: 93 +/- 23 vs. 126 +/- 20/min. Left-ventricular (LV) peak pressure was significantly decreased at the end of the reperfusion, 104 +/- 33 and 77 +/- 22 mmHg, as was dP/dtmax:2155 +/- 655 vs. 1720 +/- 895 mmHg/s. Cardiac output was insignificantly decreased at the end of reperfusion, 2.6 +/- 0.6 vs. 2.4 +/- 0.5 L/min, whereas stroke-work index exhibited a significant deterioration: 1.2 +/- 0.6 vs. 0.5 +/- 0.3 mmHg.ml/kg. LV dP/dtmin was significantly impaired after ischemia and at the end of reperfusion, -1575 +/- 385 vs. -855 +/- 310 mmHg/s, while LV end-diastolic pressure exhibited only a moderate increase: 8 +/- 5 vs. 9 +/- 3 mmHg. MVO2, in turn, remained almost constant throughout the protocol for each of two methods by which it was predicted. The results show that global work, MVO2, and external efficiency were unchanged during early and late occlusion compared to control. During the entire reperfusion the myocardium was stunned, i.e. cardiac work was decreased at maintained MVO2. Thus, external efficiency was decreased. From these results we conclude that in reperfused myocardium after cardioplegic arrest, the oxygen is only inefficiently converted to develop force.

Analysis of Variance↗

PubMed1996

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↗

PubMed1996

Analysis of respiratory water--a new method for evaluation of myocardial energy metabolism.

Aerobic ATP synthesis via oxidative phosphorylation causes a proportional production of respiratory water. Thus the amount of respiratory water produced at a given time should be a reliable measure of the current ATP demand of the mammalian myocardium. Respiratory water from isolated rabbit hearts was labeled by using the stable oxygen isotope 18O. The hearts were perfused according to the method of Langendorff (O. Langendorff. Pfluegers Arch. 61: 291-332, 1895) with 18O2-equilibrated Krebs-Henseleit solution. Control hearts were exclusively perfused with carbogen-equilibrated Krebs-Henseleit solution. Myocardial tissue was then lyophilized; the extracted water and samples from the coronary venous effluent were converted to CO2 by using the guanidine hydrochloride technique. The delta 18O values within the CO2 samples were determined by mass spectrometry and related to the standard mean ocean water (SMOW) scale. Compared with control hearts, the 18O-labeled hearts exhibited a significant increase of delta 18O values from tissue water (-47.50 +/- 0.64 vs. -40.35 +/- 2.05% SMOW; P < 0.05). The values were also significantly increased in the coronary venous effluent after a perfusion time of only 50 s (-47.50 +/- 0.64 vs. -43.66 +/- 0.91% SMOW; P < 0.05). Thus this first adaptation of the guanidine hydrochloride technique on microliter samples of myocardial tissue water and coronary venous effluent demonstrates that this method can be used to evaluate both respiratory activity and the kinetics of cardiac metabolic processes.

Adenosine Triphosphate↗

PubMed1996

Delayed recompression after SCUBA diving-induced barotrauma: a case report.

During a SCUBA course, a woman (26 yr) ascended from shallow water (< or = 8 m) in panic on 2 successive days. She suffered moderate symptoms of gas embolism (pain in the upper chest and in both knees), very likely owing to a pulmonary barotrauma. The woman remained untreated for 3 d until her return flight during which symptoms worsened. After another 24 d, she entered the hyperbaric center in Duisburg, Germany, where she was successfully treated by recompression with hyperbaric oxygenation (to 0.6 MPa on day 1, and to 0.28 MPa on days 2 and 3).

Adult↗

PubMed1996

[Effect of a new bradycardic substance on the isolated rabbit heart].

Beside wall tension and contractility, heart rate is a major determinant of myocardial oxygen consumption. Therefore, a decrease in heart rate could prevent ischemia or reduce its consequences. We examined the effect of a new bradycardic agent of the benzazepinone-type (DK-AH 269) on eight isolated, saline-perfused rabbit hearts, bradycardia resulted from a specific blockade of i(f)-channels in sinus node cells. After control measurements (C), the substance was added in three increasing concentrations (D1: 10(-8) M, D2: 10(-7) M, D3: 10(-6) M). We observed a dose-dependent reduction in heart rate (C: 206 +/- 25, D1: 195 +/- 30, D2: 77 +/- 41, D3: 154 +/- 48/min). In the highest dosage, the duration of diastole was increased by 100%. To characterize systolic function, we measured stroke volume (SV), peak left ventricular pressure (LVPmax) and its first derivative (dP/dtmax). Aortic flow was slightly decreased whereas SV increased to 108% of control after initial reduction at the two lower dosages. LVPmax remained unchanged, and dP/dtmax was dose-dependently reduced to 91, 81, and 70% of control (C: 1885 +/- 376, D1: 1721 +/- 525, D2: 1526 +/- 504, D3: 1327 +/- 337 mm Hg/s); dP/dtmin as a measure of early relaxation was also reduced. The coronary flow per beat did not change compared with control in the presence of the two lower doses of DK-AH 269, but was significantly increased with the highest dose (C: 0.29 +/- 0.06, D1: 0.28 +/- 0.07, D2: 0.29 +/- 0.09, D3: 0.34 +/- 0.11 ml). The myocardial oxygen demand was dose-dependently decreased (C: 10.4 +/- 2.5, D1: 9.6 +/- 2.5, D2: 8.8 +/- 2.6, D3: 7.9 +/- 2.4 ml/min/100 g). The relation between subendocardial and subepicardial flow, assessed with colored microspheres, exhibited no changes in the presence of the highest dose of DK-AH 269 (C: 1.28 +/- 0.09, D3: 1.27 +/- 0.08). DK-AH 269 reduced heart rate in isolated rabbit hearts and increased the duration of diastole. Whereas systolic function was primarily left unchanged, coronary flow per beat and oxygen consumption were decreased. According to our results, this new bradycardic agent could be useful in treating coronary heart disease.

Animals↗