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Biomedical subjects

W Schaper

Publications and source records attributed to W Schaper.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Cardiac function in the chronically volume-overloaded canine heart.

In the chronically volume-overloaded canine heart due to AV-block evaluations of cardiac function were performed during the development of hypertrophy and at stable hypertrophy. In an early stage (1 and 2 weeks of AV-block) when no or only a slight increase of cardiac muscle occurred, contractility measured from dP/dtmax at comparable load is elevated, while later (10 weeks of AV-block) when stable hypertrophy is present, contractility becomes again normal, In the hypertrophied heart a non-depressed cardiac performance and contractility and functional reserve was established from insitu experiments and from evaluations in the isolated heart.

Animals↗
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Influence of tachycardia on regional myocardial flow in chronic experimental coronary occlusion.

The influences of tachycardia on regional myocardial flow was studied in normal dogs and in dogs with chronic coronary artery occlusions. Coronary vasodilation was induced by coronary occlusion and subsequent release, i.e. by reactive hyperemia. Local myocardial blood flow was determined with the tracer microspheres technique. In normal hearts atrial pacing produced a slight but significant increase in coronary resistance in the subendocardial layers of the left ventricle. The coronary resistance of the subepicardium remained unaffected. In the right ventricle atrial pacing had no influence on the resistance to flow. In hearts with multiple coronary occlusions tachycardia-induced changes of coronary resistance were more pronounced. In the collateral dependent subendocardium coronary resistance increased from 0.4-2.2 resistance units when the heart rate was raised to 200 beats/min. Perfusion of the right ventricular myocardium became also rate-dependent when the right coronary artery was chronically occluded. We conclude that regional perfusion dependes upon the relationship between the effective perfusion pressure, which is reduced in chronic coronary occlusion, and the integral of effective tissue pressure, which is increased with tachycardia. The results cannot be explained by assuming excessive O2-demand but rather by a rate-induced lowered O2-supply.

Animals↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Exerimental coronary artery occlusion. III. The determinants of collateral blood flow in acute coronary occlusion.

Coronary collateral blood flow was measured with tracer microspheres in 3 different experimental conditons in the dog heart: 1. after occlusion of a large coronary artery in the in situ beating heart, 2. after occlusion of a small coronary artery in the in situ beating heart and 3. after occlusion of a large coronary artery in the isolated, empty beating, blood-perfused heart. with large coronary artery occlusion in situ, collateral blood flow was very low (5ml/min/100 g). Large coronary artery occlusion in the isolated heart showed a much higher collateral blood flow (25 ml/min/100 g). Small coronary artery occlusion in situ showed a relatively high collateral blood flow (22 ml/min/100 g). Small coronary artery occlusion produced only very small infarcts even when infarct size was expressed as the ratio of infarcted area over the area-at-risk (i.e., perfusion area of the occluded artery). Our experiments showed that acutely available collateral blood flow depends on perfusion pressure, extravascular resistance, size of the area at risk and size, number, and location of collateral vessels.

Acute Disease↗
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Dilatory capacity of the coronary circulation and its correlation to the arterial vasculature in the canine left ventricle.

The functional capacity of flow limiting myocardial conductance vessels was evaluated in canine hearts. In an isolated heart preparation transmural coronary flow distribution during maximal vasodilation was measured in the unloaded diastolic arrested left ventricle with tracer microspheres. The ratio of subendocardial versus subepicardial (ENDO/EPI) flow in the left ventricular free wall was 1.6. Measurements in 8 different wall layers showed a successive increase in maximal coronary flow from the subepicardium towards the deeper layers. A decreased subendocardial vascular resistance due to a better vascularization is forwarded as a mechanism to compensate for the extravascular compression during cardiac contraction. This statement contradicts the commonly accepted hypothesis that a diminished vascular tone with a reduction of the dilatory reserve in the subendocardium accounts for a homogeneous flow distribution in the normal beating heart. An augmentation of subendocardial supplying vessel capacity could be established from the angiographic determination of the coronary arterial volume of intramural small arteries and arterioles. From a strict parallelity in maximal coronary flow and coronary arterial volume within the wall, it becomes probable that these vascular structures are the flow-limiting factors which determine regional coronary flow reserve in the absence of extravascular compressive forces.

Animals↗
PubMedDate not supplied

The activity of xanthine oxidase in heart of pigs, guinea pigs, rabbits, rats, and humans.

We isolated and purified xanthine oxidase by Sephadex gel filtration and assayed the activity of the enzyme by urate production which we measured by HPLC and UV absorption at 290 nm. We applied this method to extracts of liver and heart of rats, guinea pigs, rabbits, and pigs and to heart of dogs and humans. We found that pig hearts do not exhibit xanthine oxidase activity and that human and rabbit hearts produced small amounts of urate only after hours of incubation. We conclude that xanthine oxidase does probably not play an important part in the mechanisms leading to myocardial infarction using the free radical generating pathway, because it is absent in one species (pig) and barely detectable in two others (rabbit and man) that are known for their rapid and complete infarction following acute coronary occlusion.

Allopurinol↗
PubMedDate not supplied

Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals.

Xanthine oxidase activities of pig myocardium and blood during and following myocardial ischemia were measured using HPLC, and electrochemical detection of hypoxanthine, xanthine and uric acid. Myocardial ischemia was produced by occluding the anterior descending coronary artery two-thirds of the way from its origin. There was no accumulation of either xanthine or urate in the ischemic pig myocardium during occlusion periods of 90 min, but there was a substantial accumulation of hypoxanthine. Similarly, there was no increase in myocardial xanthine or urate during the 30 min reperfusion following coronary artery occlusion periods of 15, 30, 60 or 90 min. Following in vitro incubation at pH 8 of myocardial homogenates or blood with either hypoxanthine or xanthine and NAD, no urate production was detectable. In contrast, significant amounts of xanthine and/or urate were produced, following addition of xanthine oxidase to the reaction mixtures. Additional in vitro experiments showed that the following pig tissues were lacking xanthine oxidase activity: left and right atrial appendage, left and right ventricle, interventricular septum, anterior descending and circumflex coronary arteries, ascending aorta, lung, and blood. Large amounts of xanthine oxidase (9.3 +/- 1.8 SEM mU/g wet weight, n = 7) were found in pig liver. In the ischemic pig heart, transmural infarction developed within 60 min of ischemia. Ventricular arrhythmias and fibrillation occurred most frequently within 45 min of ischemia and within seconds after reperfusion. These results showed that the pig heart and blood were xanthine oxidase deficient, suggesting that xanthine oxidase-derived free oxygen radicals were not involved in the cytotoxic and arrhythmogenic effects brought about by myocardial ischemia and/or reperfusion in the pig.

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Intracellular trapping of adenosine during myocardial ischemia by L-homocysteine.

Experiments were carried out to test the hypothesis whether adenosine produced by ATP catabolism during ischemia can be trapped with L-homocysteine and be re-utilized during reperfusion. During intraatrial infusion of L-homocysteine (100 mg/kg/h), the ischemic accumulation of adenine nucleosides and oxypurines in dog myocardium was found to be less than 50% of that during control ischemia. A high proportion of adenosine was recovered as S-adenosyl-L-homocysteine. On reperfusion, S-adenosyl-L-homocysteine. On reperfusion, S-adenosyl-L-homocysteine tissue content remained high. After 3 hours of reperfusion approximately 50% of the accumulated S-adenosyl-L-homocysteine were still found in the tissue. Infusion of L-homocysteine did not cause an accumulation of S-adenosyl-L-homocysteine in the nonischemic myocardial tissue. L-homocysteine treatment caused a further depletion of ATP during reperfusion after 30 minutes of ischemia, which can be interpreted as a toxic effect. We conclude that L-homocysteine is indeed able to trap adenosine produced by ATP breakdown, but the reaction is not readily reversible and is therefore not useful for quick restoration of postischemic ATP levels.

Adenine Nucleotides↗
PubMedDate not supplied

Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels.

The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/mumol/g w w/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 mumol/g w w at the 40th reperfusion vs. 6.7 mumol/g w w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.

Adenosine Monophosphate↗
PubMedDate not supplied

Experimental coronary artery occlusion. I. Measurement of infarct size.

We studied the size of infarcts in 25 dogs 48 hrs after proximal occlusion of the left anterior descending coronary artery. In one group of animals infarct size was measured by histologic criteria, in another group the infarct was measured macrohistochemically using p-NBT and malate to incubate unfixed slices of myocardium. In both groups infarct size was expressed as percentage of the area of perfusion of the occluded artery. Infarct size was 72% of the area-at-risk in the group studied by histology and 74.5% in the macrohistochemical group. The satisfactory agreement of both methods favors the p-NBT technique because of its ease and speed. It is suggested that the expression of infarct size as percentage of the perfusion area is a good definition and should be used in experiments designed to manipulate infarct size. In this way differences in the size of occluded arteries and their respective perfusion areas have no or only a negligible influence on infarct size.

Animals↗
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Relation between lipolysis and glycolysis during ischemia in the isolated rat heart.

The relation between lipolysis and glycolysis during ischemia was investigated in isolated perfused rat hearts. In hearts perfused with 11 mM glucose, ischemia caused a marked increase of glycerol release from 10 to 33 nmol/g wt weight/min. Substrate-free perfusion induced an initial stimulation of glycerol release, but lipolysis was subsequently reduced to values comparable to normoxic conditions. Neither did perfusion in the presence of acetate (10 mM) and beta-hydroxybutyrate (10 mM) stimulate lipolysis. Inhibition of glycolysis by pyruvate prevented the increase of glycerol release during ischemia. These data suggest a tight link between glycolysis and lipolysis during ischemia which is probably mediated by the availability of glycolytically produced glycerol-3-phosphate for reesterification. In the absence of glycerol-3-phosphate, the lipolysis is regulated by product inhibition. As a consequence, the tissue triglyceride levels after perfusion remained fairly constant in all groups of hearts. The calculated energy loss by the reesterification cycle during ischemia was found to be approximately 2.5% of the total energy production. These data are inconsistent with the assumption that this energy loss contributes significantly to the negative energetic balance of the heart during ischemia. Removal of fatty acids by reesterification may constitute a protective mechanism in order to prevent excessive intracellular accumulation of fatty acids and derivative esters during ischemia.

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Experimental occlusion of two small coronary arteries in the same heart. A new validation method for infarct size manipulation.

A method for the evaluation of interventions aimed at manipulation of infarct size is described. This method has 2 advantages over other methods: 1. Two small-to-medium sized coronary branches of the same heart are occluded and reperfused in sequence. Thereby a "control-infarct" can be compared with a "test-infarct", both within the same heart. 2. The amount of infarcted tissue in both areas is quantitated by using the p-NBT method. A condition of the method is that the areas of perfusion of both arteries are equal. Infarct size is always expressed as a percentage of the perfusion area of the occluded artery. Validation experiments with simultaneous occlusion and reperfusion of both arteries resulted in infarcts of equal size. Validation experiments with regard to the p-NBT method showed that reperfusion accelerates the washout of dehydrogenases from infarcted tissue which allows early and precise diagnosis of infarcts after relatively short occlusion- and reperfusion periods.

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