Endogenous beta-galactosidase expression in murine pancreatic islets.
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Animals↗
Biomedical subjects
C Nienaber
Publications and source records attributed to C Nienaber.
NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study.
BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.
Aged↗
Analysis of gene expression patterns in small amounts of human ventricular myocardium by a multiplex RNase protection assay.
End-stage human heart failure is associated with changes in expression of steady-state messenger RNA (mRNA) levels. These changes correspond to alterations in protein levels and myocardial function and may have clinical implications regarding etiology, clinical state, or prognosis. However, analysis of mRNA levels in endomyocardial biopsies can be accomplished only by the quantitative polymerase chain reaction, which is difficult to standardize. The aim of the study was to evaluate whether the RNase protection assay is applicable to measure mRNAs of multiple genes simultaneously in small amounts of ventricular myocardium comparable to myocardial biopsies. Total RNA was prepared from left ventricular myocardium from terminally failing hearts with idiopathic (n=9) or ischemic cardiomyopathy (n=7) and from nonfailing control hearts (n=10). mRNA was measured by an optimized RNase protection assay for the beta1-adrenoceptor, the stimulatory G protein alpha-subunit (Gsalpha), phospholamban, the calcium ATPase of the sarcoplasmic reticulum (SERCA), beta-myosin heavy chain (beta-MHC), and the atrial natriuretic peptide (ANP). We extracted 10.7+/-2.1 microg total RNA from three myocardial biopsies taken in vitro. All of the six genes were measurable in duplicate in a total of 7 microg RNA. mRNAs of beta1-adrenoceptor, phospholamban, and SERCA were lower in failing than in nonfailing myocardium by 50%, 33%, and 42% respectively, whereas beta-MHC and Gsalpha mRNAs were unchanged. mRNA of ANP was expressed at high levels only in the failing myocardium, providing a highly specific and sensitive marker for discriminating nonfailing and failing hearts. A direct comparison with ANP and Gsalpha levels obtained by Northern blot analysis with 7.5 microg total RNA showed a good correlation between the two methods. The RNase protection assay is thus a suitable method for simultaneous measurements of multiple mRNA levels in human myocardial biopsies. Changes in mRNA levels closely reflected those identified by other methods using larger amounts of RNA. Increased myocardial ANP mRNA levels determined by the RNase protection assay may serve as a molecular marker of heart failure.
Adolescent↗
Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice: comparison with wall motion and technetium-99m sestamibi single-photon emission computed tomography. The Nycomed NC100100 Investigators.
OBJECTIVES: We sought to assess the feasibility and accuracy of myocardial contrast echocardiography (MCE) using standard imaging approaches for the detection of perfusion defects in patients who had a myocardial infarction (MI). BACKGROUND: Myocardial contrast echocardiography may be more versatile than perfusion scintigraphy for identifying the presence and extent of perfusion defects after MI. However, its reliability in routine practice is unclear. METHODS: Fundamental or harmonic MCE was performed with continuous or triggered imaging in 203 patients with a previous MI using bolus doses of a perfluorocarbon-filled contrast agent (NC100100). All patients underwent single-photon emission computed tomography (SPECT) after the injection of technetium-99m (Tc-99m) sestamibi at rest. Quantitative and semiquantitative SPECT, wall motion and digitized echocardiographic data were interpreted independently. The accuracy of MCE was assessed for detection of segments and patients with moderate and severe sestamibi-SPECT defects, as well as for detection of patients with extensive perfusion defects (>12% of left ventricle). RESULTS: In segments with diagnostic MCE, the segmental sensitivity ranged from 14% to 65%, and the specificity varied from 78% to 95%, depending on the dose of contrast agent. Using both segment- and patient-based analysis, the greatest accuracy and proportion of interpretable images were obtained using harmonic imaging in the triggered mode. For the detection of extensive defects, the sensitivity varied from 13% to 48%, with specificity from 63% to 100%. Harmonic imaging remained the most accurate approach. Time since MI and SPECT defect location and intensity were all determinants of the MCE response. The extent of defects on MCE was less than the extent of either abnormal wall motion or SPECT abnormalities. The combination of wall motion and MCE assessment gave the best balance of sensitivity (46% to 55%) and specificity (82% to 83%). CONCLUSIONS: Although MCE is specific, it has limited sensitivity for detection of moderate or severe perfusion defects, and it underestimates the extent of SPECT defects. The best results are obtained by integration with wall motion. More sophisticated methods of acquisition and interpretation are needed to enhance the feasibility of this technique in routine practice.
Contrast Media↗
Results of transmyocardial laser revascularization in non-revascularizable coronary artery disease after 3 years follow-up [ssee comments].
BACKGROUND: Transmyocardial laser revascularization is a new therapeutic option for end-stage coronary artery disease if no other cardiological or cardiosurgical intervention is possible. Data are few on how patients fare after more than 1 year follow-up. METHODS AND RESULTS: From a total of 157 patients who were suggested for transmyocardial laser therapy in the years 1995-1997, 126 were judged to have non-revascularizable coronary artery disease (mean age 61.9 +/- 14 years, 80% men, mean left ventricular ejection fraction 46.2 +/- 17.1%). Sixty-six patients had a good clinical response to intensification of the antianginal therapy and were therefore treated further medically. In 60 patients with refractory angina, sole transmyocardial laser revascularization without cardiopulmonary bypass or additional grafts was performed. The transmyocardial laser revascularization group was 32% female; 78.3% patients had had bypass operations; the mean left ventricular ejection fraction was 53.6 +/- 15%. Eighty five percent of the transmyocardial laser revascularization patients had demonstrable ischaemic regions, as visualized by dipyridamol-MIBI scintigraphy. The percentage of patients with some hibernating myocardium in positron emission tomography studies was 70%. Good early relief of angina symptoms was experienced by patients who had undergone laser treatment. After 3 months the Canadian Cardiovascular Society class fell from 3.31 +/- 0.51 to 1.84 +/- 0.77 in 49 patients (P < 0.0001), but increased in the total group to 2.02 +/- 0.92 after 6 months (n = 47), to 2.26 +/- 0.99 after 1 year (n = 42), to 2.47 +/- 1.11 after 2 years (n = 38) and to 2.58 +/- 0.9 after 3 years (n = 19). MIBI/positron emission tomography data at rest and after 6 months was worse in patients in whom pre- and postoperative studies were complete (n = 22). The peri-operative mortality was 12% (n = 7: peri-operative myocardial infarction, low output syndrome, arrhythmia). Mortality after 1 and 3 years was 23% and 30%, respectively. The risk of transmyocardial laser revascularization was significantly elevated in patients with left ventricular ejection fraction < 40%. Late deaths (n = 9) were due to sudden arrhythmias or pump failure. There was a high rate of cardiac events and reinterventions in the transmyocardial laser revascularization group, including percutaneous transluminal coronary angioplasty in newly developed lesions (n = 7), valve replacement (n = 2), need for intermittent urokinase therapy (n = 5) and heart transplantation (n = 2). CONCLUSION: Fifty percent of patients with non-revascularizable coronary artery disease submitted for transmyocardial laser revascularization can be stabilized medically. Transmyocardial laser revascularization led to a rapid early relief of symptoms, but with a trend towards worsening over time and showed a high peri-operative risk (> 10%) dependent on the pre-operative ejection fraction. Our data were in contrast to other published reports on the more beneficial effects of transmyocardial laser revascularization and should lead to further investigation of this experimental method. Transmyocardial laser revascularization should only be performed after failure of maximal anti-anginal therapy, and should be avoided when the left ventricular ejection fraction is < 40%.
Coronary Disease↗
Acute pulmonary embolism: value of transthoracic and transesophageal echocardiography in comparison with helical CT.
OBJECTIVE: The goal of this study was to prospectively compare the accuracy of transthoracic and transesophageal B-mode and Doppler echocardiography with helical CT for detecting acute pulmonary embolism. SUBJECTS AND METHODS: Thirty-five consecutive patients underwent transthoracic and transesophageal echocardiography and contrast-enhanced helical CT. Echocardiographic examinations were analyzed for indirect criteria, including increased main pulmonary artery diameter, tricuspid regurgitation, and dilatation of the right ventricular cavity, as well as for direct thrombus visualization. Sensitivity, specificity, and negative and positive predictive values were calculated. RESULTS: Pulmonary embolism was revealed by helical CT in 22 of 35 patients; in 11 of these 22 cases, central pulmonary embolism was seen. Transthoracic and transesophageal B-mode echocardiography failed to reveal pulmonary embolism in nine patients, two of whom had central pulmonary embolism. The sensitivity and specificity of the combination of both echocardiographic investigations were 59% and 77% respectively (82% and 92% for central pulmonary embolism). In three patients, pulmonary embolism was diagnosed by direct clot detection with transesophageal echocardiography. In two patients, only the indirect parameters indicated pulmonary embolism. Overall indirect echocardiographic parameters were characterized by a low sensitivity that ranged from 50% for tricuspid regurgitation to 21% for main pulmonary artery diameter. CONCLUSION: In comparison with helical CT, transthoracic and transesophageal echocardiography had limited accuracy for detecting pulmonary embolism.
Acute Disease↗
[Collagen application after arterial puncture].
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Administration, Topical↗
Detection of coronary artery disease with positron emission tomography and rubidium 82.
Myocardial blood flow was evaluated in 31 subjects with not only visual but also, for the first time, circumferential profile analysis of rubidium 82 (82Rb) images acquired with positron emission tomography. Fifteen were control subjects and 16 subjects had significant coronary artery disease, defined as 50% or greater diameter stenosis in a major coronary artery or a first-order branch. Simultaneous 82Rb images at three myocardial levels were obtained before and after intravenous dipyridamole plus handgrip stress. In patients with significant coronary artery disease, visual analysis correctly identified significant disease in 26 (76%) of 34 arteries and its absence in 12 (86%) of 14 normal arteries. According to circumferential profile analysis, these numbers were 91% and 86%, respectively. Thus circumferential analysis of 82Rb images, obtained before and after intravenous dipyridamole plus handgrip stress, yielded improved sensitivity and comparable specificity compared with visual analysis.
Coronary Disease↗
Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.
BACKGROUND: Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS: On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS: In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.
Coronary Angiography↗
Development of N-butyl-N-(hydroxybutyl)-nitrosamine-induced tumors in the partially resected, proliferating rat urinary bladder in dependence upon the time of onset of stimulated DNA synthesis.
Tumor development was investigated in the partially resected, proliferating urinary bladder of rats in dependence upon the onset of stimulated de novo DNA synthesis related to carcinogen dosing. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) was used as carcinogen and administered by gavage in three fractionated doses (100 mg/kg body weight each) either during the phase of the most pronounced proliferation of the urothelium 30, 45 and 70 h after one-third resection of the bladder or 24 h and 1 week prior to partial cystectomy. When BBN was given during most increased DNA synthesis subsequent to one-third resection, the incidence of bladder tumors was reduced to 8.7% compared with 19.6% found in control animals with a non-resected, quiescent bladder. Tumor formation was neither inhibited nor enhanced when BBN was initially administered, followed by partial cystectomy 24 h or 1 week after the last carcinogen dose, yielding tumor incidences of 18.2% and 22.5%, respectively. Thus, the feeding of BBN during the period of maximum DNA synthesis inhibited tumor development in the partially resected bladder, while stimulation of cell replication subsequent to carcinogen administration did not influence the carcinogenic process initiated. The results obtained indicate that time of onset of stimulated DNA synthesis related to carcinogen dosing is the decisive factor in modifying urothelial carcinogenesis in the proliferating urinary bladder.
Animals↗
Emery-Dreifuss muscular dystrophy: disease spectrum and differential diagnosis.
We report six patients with Emery-Dreifuss muscular dystrophy (EDMD) and four patients including one female with EDMD phenotype (EDMDP). This series includes one sporadic case who had previously been reported in this journal under the diagnosis of "rigid spine syndrome" in 1977. Time of observation ranged from three to ten years. Detailed cardiological assessment was performed in all patients, skeletal muscle biopsies were obtained from 9 out of 10 and cardiac muscle biopsies from 2 out of 10 patients. One patient showed evidence of cardiomyopathy in the absence of clinically apparent neuromuscular disease and one sibling of another EDMD patient reportedly had a similar combination of symptoms which, to our knowledge, has not yet been reported. Cardiac involvement was found to consist of four independent, albeit often combined features: 1) impairment of impulse generating cells; 2) conduction defects with atrial preponderance; 3) increased atrial and ventricular heterotopia; and 4) functional impairment of ventricular myocardium. Ventricular involvement as apparent from ventricular heterotopia, abnormal enddiastolic diameter, decrease of contractility and/or morphological evidence of ventricular myocardial disease was found in 7 out of 10 patients and confirmed by myocardial histopathology in two EDMD patients. In one myocardial biopsy extensive accumulations of intermediate filaments were observed, a rare finding, which has not been linked to EDMD before. Skeletal muscle biopsies showed evidence of myopathy throughout but several equivocal features such as fibre type grouping in EDMD and fibre type disproportion in EDMDP were also observed. The variability of clinical manifestation of both cardiac and neuromuscular disease encompassed a broader spectrum than apparent from the literature. The consequences for the inherent differential diagnosis are discussed.
Adolescent↗
Validation of PET-acquired input functions for cardiac studies.
To validate the determination of the arterial input function by noninvasive dynamic PET imaging, measurements of blood-pool activity in canine LV by PET were compared to beta probe measurements of arterial blood withdrawn directly from the LV. PET scans were done during intravenous bolus injections of [13N]ammonia or 82Rb, while the activity of blood withdrawn continuously from a catheter inserted in the LV was measured with a beta probe. PET determinations of LV blood-pool activity were compared with dispersion-corrected beta probe time-activity curves. In 15 experiments involving four dogs under a wide range of physiologic conditions, LV time-activity curves obtained with PET matched well in shape with those obtained with the beta probe. Linear regression yielded slopes within 10% of unity (95% confidence interval) and high correlation (r greater than 0.968, p less than 0.001). We conclude that noninvasive measurement of the arterial input function by dynamic PET imaging is valid.
Ammonia↗
[Comparison of the acute hemodynamic effect of nisoldipine (Bay k 5552) and nifedipine in patients with ischemia-induced left ventricular impaired function].
Calcium channel blockers of the dihydropyridine type have different sites of action that may cause negative inotropic effects in some patients; therefore, their use as systemic vasodilators in left heart failure may be limited. In 10 patients with coronary heart disease we compared the acute peripheral and central hemodynamic effects of i.v. nisoldipine vs. i.v. nifedipine intraindividually, using a sequential crossover protocol. All patients were subjected to right heart catheterization, arterial pressure monitoring, and simultaneous radionuclide angiography. The infusion of either calcium channel blocker was titrated to a similar steady-state reduction of mean arterial pressure by 15 +/- 3% and 15 +/- 2%, respectively, which reduced systemic vascular resistance by 25 +/- 5% and 17 +/- 2%, respectively. The required equally effective dosage was 0.17 +/- 0.06 micrograms/min/kg for nisoldipine and 0.58 +/- 0.1 micrograms/min/kg for nifedipine. In contrast to nifedipine, the administration of nisoldipine was associated with an increase in cardiac index by 0.45 +/- 0.33 l/min/m2 (p less than 0.05), stroke volume index by 3.91 +/- 3.0 ml/m2 (p less than 0.05), and left ventricular ejection fraction by 4.6 +/- 2.8% (p less than 0.05). Mean pulmonary capillary wedge pressure decreased with nisoldipine from 11.8 +/- 3.4 to 8.0 +/- 3.4 mm Hg (p less than 0.005) and mean pulmonary artery pressure decreased from 20.4 +/- 4.06 to 16.1 +/- 3.2 mm Hg (p less than 0.005), but was unaffected by nifedipine. Left and right ventricular endsystolic and enddiastolic volumes were not significantly altered by either drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog.
Recovery of adenosine triphosphate after myocardial ischemia is limited by the slow adenine nucleotide de novo synthesis and the availability of precursors of the nucleotide salvage pathways. We determined the adenine nucleotide de novo synthesis in the dog by infusion of [14C]glycine and the acceleration of adenine nucleotide built up by intracoronary infusion of ribose together with [14C]glycine or radiolabeled 5-amino-4-imidazolcarboxamide riboside or adenosine in the same animal model and with the same dosage of substrates (9 mmol) in postischemic and nonischemic myocardial tissue. After 45 minutes of occlusion of a side branch of the left coronary artery, the ischemic area was reperfused for 3 hours, and needle biopsies were taken for biochemical analysis. Adenine nucleotide de novo synthesis was found to be very slow (1.5 nmol/g wet weight per hour). The rate was doubled after ischemia. Adenine nucleotide synthesis was accelerated 5-fold by ribose, the basic substrate of the adenine nucleotide de novo synthesis, 9-fold by 5-amino-4-imidazolcarboxamide riboside, an intermediate of the adenine nucleotide de novo synthesis and 90-fold by adenosine, a substrate of the nucleotide salvage pathway. Therefore, only adenosine infusion resulted in a measurable increase of adenosine triphosphate levels after 3 hours of reperfusion, but over a longer time period, ribose or 5-amino-4-imidazol-carboxamide riboside also can be expected to replenish reduced myocardial adenosine triphosphate faster than adenine nucleotide de novo synthesis. Studies with radiolabeled 5-amino-4-imidazol-carboxamide riboside showed significant incorporation of radioactivity into 5-amino-4-imidazol-carboxamide ribose triphosphate which had also risen measurably during 5-amino-4-imidazol-carboxamide ribose infusion, and which is not normally found in heart muscle.
Adenosine↗
[Right atrial thrombus formation following transvenous catheter ablation of the AV conduction system].
A case is reported in which the formation of a right atrial mass was detected by two-dimensional echocardiography 3 weeks after successful transvenous electrical ablation of the atrioventricular junction had been performed. The mass was attached to the atrial septum at the site where the electrode catheter used for the ablation had been located and it exhibited no mobility. It was interpreted as a right atrial thrombus induced by the ablation procedure. Although no pulmonary embolic events have been observed during a 7-month follow-up period, right atrial thrombus formation must be considered as a potentially dangerous complication of transvenous catheter ablation to control supraventricular arrhythmias.
Adult↗
The importance of the collateral circulation for myocardial survival.
In acute coronary occlusion the survival time of ischemic myocardium depends critically upon collateral blood flow and on oxygen uptake at the moment of, and during, occlusion. There are good reasons to believe that ischemic myocardium provides the stimulus for near-maximal vasodilation of collateral blood vessels. Under these conditions the determinants of collateral blood flow are: a) the anatomically fixed hydraulic resistance of the collaterals proper, b) the arterial driving pressure, c) extravascular resistance (radial stress, pressure transmission across the LV wall, tissue pressure) and d) size of the ischemic bed. Under ideal conditions (maximal dilation of collaterals) overall collateral resistance is 3.5 resistance units, i.e. theoretically a perfusion pressure of 350 mmHg is needed to drive 100 ml of blood per minute through 100 g of tissue. Small ischemic beds receive a relatively larger amount of collateral flow and vice versa. This delays necrosis (but does not prevent it) following occlusion of small coronary arteries. The reason for this is the more favorable ratio of epicardial circumference (of the ischemic area) to ischemic volume because canine collaterals are exclusively located on the epicardial surface.-Tissue pressure in acute occlusion is distributed in such a way that subendocardial collateral flow is lower than subepicardial flow. This leads to an earlier onset of irreversible damage in the subendocardium, earlier damage to subendocardial microvessels, i.e. earlier subendocardial no-reflow phenomenon. Flow "offered" to but not "taken" by the subendocardium is at the disposal of the subepicardium which thereby increases its chances of survival. As a rule subendocardial flow decreases as a function of time after occlusion and subepicardial flow increases. In certain cases even subepicardial flow is too low shortly after occlusion. In this case it decreases further with time and a truly transmural infarct develops.
Animals↗
Development of collaterals. Application of external subcritical fixed constrictors in a canine model.
A canine model for a standardized induction of collaterals is presented with a fixed external constrictor that is not designed to induce an occlusion of the coronary artery and at least over the timespan of 6 weeks does not impair perfusion under resting conditions in the myocardium-at-risk. The coronary constriction was standardized by a reduction of the postocclusive reactive hyperemia of 50%. Flow measurements were performed by flowmeter and by radioactive microspheres acutely and after an interval of 6 weeks of constriction. The results showed an increase of the collateral flow from 21.2 +/- 11.8 ml/100 g/min-1 to 42.8 +/- 16.2 ml/100 g/min-1 (p less than 0.05). The regional perfusion exhibited a transmyocardial gradient in favour of the subepicardial layers with 49.3 +/- 25 ml/100 g/min-1 as compared to 33.1 +/- 17.3 ml/100 g/min-1 (p less than 0.05) of the endocardial layers. Reactive hyperemia, as determined by flowmeter, was decreased by 21% after 6 weeks on account of slow progression of the coronary constriction due to intimal reactions, whereas reactive hyperemia, as determined by the microsphere method, increased by 9% due to additional collateral channels.
Animals↗
The relationship between the perfusion deficit, infarct size and time after experimental coronary artery occlusion.
It is well known that coronary occlusions of short duration do not produce infarcts in the dog heart, but permanent occlusions always do. The aim of this paper was to investigate with quantitative direct measurements the determinants of infarct size within these two extremes. We measured left ventricular MV2, coronary and collateral blood flow and infarct size after occlusion times varying between 45 minutes and 24 hours. MVO2 was kept low in one group by establishing low heart rates with a synthetic opiate. In another group, MV2 was kept elevated by giving synthetic catecholamines (dobutamine) that stimulated contractility and heart rate. Under the described experimental conditions LV-coronary blood flow reflected the true demand for blood and oxygen. The ratio of collateral blood flow over coronary blood flow (both measured with tracer microspheres) was therefore a good approximation of the supply-demand ratio (SD). Since collateral flow was inhomogeneously distributed across the left ventricular wall, the SD-ratio showed similar variations. As the collateral blood flow increased with elapsed time after coronary occlusion, the SD-ratio improved. Since high LV-O2-demand increased coronary flow but exerted practically no influence on collateral flow, this situation influenced the SD-ratio in a negative way. Decreased O2-demand had the opposite effect. The SD-ratio is thus a valid expression of the relative and absolute blood flow deficit as influenced by the local and general O2-demand. We found significant and characteristic correlations between the SD-ratio and infarct which was only influenced by time. A blood flow deficit of 90% (i.e., collateral flow = 10% of required flow) produced a 50%-infarct (relative to the risk-region) with a 45-min occlusion but a 90%-infarct with occlusion times of 3 hrs and longer. If the perfusion deficit is only 0.5 (collateral flow = 50% of required flow), no infarct is detectable at occlusion times shorter than 3 hrs. Small perfusion deficits of only 20% below required flow caused infarctions at 24 hrs and longer. In the group where the SD-ratio was closer to unity because of a low overall LV-O2-consumption (bradycardia), infarcts at t = 24 hrs were significantly smaller than in the group with a high LV-MVO2.
Animals↗