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Biomedical subjects

W Schaper

Publications and source records attributed to W Schaper.

At least 163 records · Page 9Linked to original sources
PubMed1983

Thrombolysis in acute experimental myocardial infarction.

Lysis of thrombi by intracoronary application of streptokinase has become a new therapeutic approach in patients with acute myocardial infarction. To simulate the clinical situation of myocardial infarction a new experimental model was developed, which was based on a thrombotic coronary occlusion at the site of a high degree stenosis created by a constrictor. In 20 dogs, two ligations 15 mm apart were prepared at the left anterior descending or circumflex coronary artery. After closure of the distal ligation, 2 IU of thrombin was injected through a catheter directly in front of the proximal ligation. The catheter was withdrawn and the proximal ligation was closed. Occlusion time ranged from 1 to 6 hours. At 1, 2, 4 and 6 hours after occlusion, streptokinase was infused for 1 hour (100,000 IU in 200 ml of saline solution) into the left main coronary artery. Hemodynamic variables and coronary blood flow to the ischemic and normal myocardial areas were recorded continuously. Myocardial perfusion was measured six times with tracer microspheres. Reinstatement of blood flow, as well as normalization of myocardial perfusion in the ischemic area, was achieved by streptokinase at 5 minutes after 1 hour of occlusion, 8 minutes after 2 hours, 15 minutes after 4 hours, and 30 minutes after 6 hours; no hyperemic flow occurred. Postmortem staining of infarct size revealed more than 50% of viable myocardium in the perfusion area of the thrombotic vessel even after 6 hours of occlusion. Hemorrhage occurred only after 6 hours of occlusion and was limited to the central area of necrosis in the subendocardial layer. Serious reperfusion arrhythmias occurred only after 1 and 2 hours of occlusion and seemed to be independent of the mode of reperfusion; however, the total number of episodes of ventricular fibrillation after reperfusion was probably decreased compared with that after sudden and hyperemic reflow.

Animals↗
PubMed1983

Reperfusion of ischemic myocardium: ultrastructural and histochemical aspects.

The effects of reperfusion on ischemic myocardium generally depend on the severity of the preceding ischemic injury. Reperfusion of myocardium, irreversibly injured by ischemia, produces further progression of myocardial necrosis that is accompanied by simultaneously occurring stimulation of interstitial cell proliferation resulting in scar formation. Reperfusion of reversibly injured myocardium leads to structural improvement and reorganization. Thus, it may be stated from the ultrastructural part of this study that reperfusion of ischemic myocardium induces 1) slow structural recuperation after reversible injury, and 2) accelerated cellular destruction and symptoms of scar formation after irreversible ischemic injury. We observed that the reduced tissue content of nicotinamide adenine dinucleotide (NAD), rather than reduced dehydrogenase activity, is the basis of histochemical reactions employing tetrazolium salts. Directly measured NAD tissue content in ischemic tissue correlated well with the degree of ultrastructural injury and with macroscopic differential staining. Occlusion of two small coronary arteries in the same heart followed by reperfusion of only one artery (identical occlusion times for both arteries) showed identical infarct sizes for reperfused and nonreperfused myocardium for occlusion times of 3 and 6 hours. When the effects of occlusion times of less than 3 hours are studied with tetrazolium salts, a difficult technical problem arises: during that time, tissue-NAD concentrations have not decreased enough to enable differential staining. Reperfusion leads to washout of NAD, thus producing differential staining; this may be a harmful effect of reperfusion. However, because early reperfusion leads to significant structural and functional recovery and to small infarcts, reperfusion injury is unlikely to occur. Both ultrastructural and histochemical evidence suggest that reperfusion is beneficial for reversibly injured tissue but accelerates the decay of irreversibly injured tissue.

Animals↗
PubMed1983

Ultrastructural correlates of reduced cardiac function in human heart disease.

The ultrastructural correlates of a decrease in cardiac function resulting in heart failure are unknown. For this reason, transmural needle biopsies were taken during cardiac surgery from patients with aortic valve disease (AD, n = 143) and coronary heart disease (CHD, n = 136) and examined by electron microscopy. Ultrastructural features were: occurrence of abnormal but still viable nuclei and mitochondria combined with lack of myofibrils in greatly enlarged myocardial cells plus an increased amount of fibrosis in patients with AD. In CHD most myocardial cells were of normal size or atrophic, reduced in number and showed signs of subcellular degeneration. Fibrosis was greatly increased. These findings were confirmed in both groups of patients by quantitative analysis (morphometry). Cardiac failure was diagnosed and clinically treated in about 25% of all patients investigated in this study. The loss of specific myocardial cellular components or loss of entire cells are the morphological correlates of cardiac failure in different types of heart disease.

Aortic Valve Insufficiency↗
PubMed1983

Natural defense mechanisms during ischemia.

Mechanisms are described that are known to prolong survival of ischemic myocardium. Some of these mechanisms are species-specific: collateral blood flow does not contribute to survival in rats, rabbits, and pigs but it salvages subepicardial myocardium in the dog and probably in man. The most important defense mechanism is enlargement of collaterals by growth of pre-existing smaller vessels. This process is not operative in sudden coronary occlusion but may save a substantial portion of the myocardium if occlusion occurs more slowly, i.e. several days up to a week. Experimental evidence is presented that thrombotic occlusion, clot-retraction, and partial clot lysis by endothelium can be sufficiently dynamic to allow intermittent myocardial perfusion and to permit collaterals to grow. The glycogen stores of the heart are of limited importance. They are useful for glycolytic ATP-production, the limitation is imposed by the inhibition of glycolysis in ischemia due to unfavourable pH and lack of NAD. Some beta-blockers do interfere with glycogenolysis in the heart. The cardioprotective role of adenosine needs further study. An interesting concept is the change in resistance to ischemia after repeated cycles of ischemia. It is not known at present whether repeated cycles will increase or decrease the myocyte's resistance against ischemia.

Adaptation, Physiological↗
PubMed1982

Effect of intraaortic balloon counterpulsation (IABP) on myocardial infarct size and collateral flow in an experimental dog model.

To determine the influence of IABP on infarct size and collateral blood flow in each of 12 openchest anaesthetised mongrel dogs two small branches of the left coronary artery were occluded consecutively. The perfusion areas of both branches were comparable in size. IABP was started immediately before ligation of the first branch for a 90-min period followed by a reperfusion period of 90 min. Subsequently the second vessel was also occluded for 90 min as a control without IABP while myocardial oxygen consumption remained constant and was then reperfused. Infarct size was expressed as a percentage of the perfusion area. A difference in infarct size with and without IABP (18 +/- 17, 18 +/- 10% respectively) could not be observed. However a significant increase of collateral blood flow due to IABP in the subendocardial layer from 8.9 +/- 4.8 to 14.9 +/- 4.6 ml/100 g/min (p less than 0.05) was prevalent. In the subepicardial layer the augmentation from 23.7 +/- 19.9 to 26.9 +/- 15.2 was not significant. Thus, in spite of a small increase of collateral blood flow in the subendocardial layer of the ischemic myocardium the infarct size was not reduced by IABP in our dog model.

Animals↗
PubMed1982

DNA synthesis in coronary collaterals after coronary artery occlusion in conscious dog.

With [3H]thymidine, DNA synthetic activity in coronary collateral arterioles was assessed in dogs subjected to progressive stenosis of the left circumflex coronary artery for different periods (36 h-5 days). Coronary flow, reactive hyperemia, and pressure gradient (aortic pressure, peripheral coronary pressure) were measured. Normal animals and animals with sham operations served as controls. Labeling of nuclei was seen in seven of the constricted dogs. Proliferative activity was highest at the level of the smallest diameters of the collateral vessels (midzone). There was heavy labeling in intima and media. Adventitial and myocardial mesenchymal cells also incorporated [3H]thymidine. No radioactive DNA was found in control animals. The data suggest that the active growth process in collaterals after constriction of the left circumflex coronary artery appears early, as there is evidence of collateral growth after 36 h of constriction. Peak growth as evidenced by [3H]thymidine incorporation was reached when the occlusion period was 4 days.

Animals↗
PubMed1982

Influence of physical exercise on coronary collateral blood flow in chronic experimental two-vessel occlusion.

In 45 approximately 1-year-old purebred German shepherd dogs, the left circumflex and the right coronary arteries were chronically occluded by implantation of slowly swelling ameroid constrictors. Before the operation, 27 dogs were trained on a treadmill until they could run 8 mph on a 22% incline for 1 hour, 5 days per week. Two weeks after the operation, exercise was gradually resumed and continued for 4 weeks, until the preoperative fitness level had been regained. Preoperative exercise training lasted 1-3 months; postoperative training lasted 100 +/- 22 days (mean +/- SD). After the dogs had trained with two chronically occluded coronary arteries, collateral and coronary blood flows were measured with tracer microspheres at maximal coronary vasodilation (adenosine infusion) in an isolated, blood-perfused Langendorff preparation at perfusion pressures of 40, 60, 80, 100, 120 and 140 mm Hg. Eighteen nonexercising dogs that also had two-vessel coronary occlusion served as controls. Nine controls and nine exercising dogs were paired littermates. Exercise of relatively high intensity (heart rates greater than 200 beats/min) before and after occlusion had no effect on coronary collaterals. Collateral conductance in trained and untrained dogs reached only slightly less than 40% of that of the replaced coronary artery. This result agrees well with earlier results in a group of nonexercising dogs with chronic two-vessel occlusion studied in an identical way. Two-vessel occlusion was associated with a 25% mortality rate. All dogs died instantaneously without warning symptoms of ventricular fibrillation. Exercise had no influence on mortality.

Animals↗
PubMed1982

Native collaterals in the development of collateral circulation after chronic coronary stenosis in mongrel dogs.

The response of native collateral circulation to chronic stenosis of the left circumflex coronary artery (LCx) was studied in 17 mongrel dogs. Stenosis restricted reactive hyperemia of the LCx without affecting resting flow. Regional myocardial blood flow was measured by the tracer microsphere technique. Coronary collateral blood flow to the LCx was determined during maximal reactive hyperemia of the left anterior descending branch before and 5 weeks after implantation of a fixed LCx stenosis in the open-chest preparation. The protective effect of collaterals was tested by LCx ligation 5 weeks after implantation of stenosis. Presence of acute myocardial infarction was determined by nitroblue tetrazolium staining. Eleven dogs had a myocardial infarction (group A), but six dogs showed no evidence of infarction at autopsy (group B). In group A, collateral flow and minimal coronary resistance of the LCx bed changed little after LCx stenosis, from 12 to 15 ml/min/100 g and from 10.5 to 10.0 mm Hg/ml/min/100 g, respectively (both p less than 0.05). In contrast, collateral flow in group B increased from 22 to 102 ml/min/100 g (p less than 0.05), and minimal coronary resistance of the LCx bed decreased from 4.8 to 1.4 mm Hg/ml/min/100 g (p less than 0.01). Group A had lower native collateral flow (p less than 0.05) and higher native minimal coronary resistance of the LCx bed than group B (p less than 0.05). Postobstructive LCx pressure correlated well with blood flow data. The LCx risk region was of comparable size in groups A and B, 36.4% vs 39.0% of total left ventricle (p greater than 0.05). Two responses of collateral circulation to chronic stenosis were documented: lack of collateral growth in group A, but significant collateral growth in group B. The natural variation of collateral circulation was the major determinant of the different responses that were important with stenosis of a major coronary artery.

Animals↗
PubMed1981

Biochemical mechanism of infarct size reduction by pyruvate.

We have explored the biochemical mechanism of the infarct size reduction found after intracoronary pyruvate infusion. Using the double infarct model, we simultaneously produced in nine dogs a control- and a therapy-infarct and compared the infarct sizes in each dog after 90 min of occlusion and 90 min of reflow. Intracoronary pyruvate reached the therapy infarct only by way of collaterals but had no access to the control infarct. Tissue levels of reduced nicotinamide dinucleotide (NADH) were measured in control-normal-, therapy-normal-, control-ischaemic-and pyruvate-treated ischaemic areas. In all nine dogs we found a significant reduction in infarct size and NADH levels in the pyruvate-treated areas. Therapy-normal NADH levels fell to 30+/-10% (mean+/-SD) of control-normal levels and therapy-ischaemic NADH levels to 26+/-17% of control-ischaemic levels. We assumed that the infused pyruvate was converted to lactate and at the same time NAD was generated from NADH. Thereby the blockage of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) by high NADH/NAD-ratios in ischaemic myocardium should be moderated, and ATP production by anaerobic glycolysis stimulated. These small amounts of ATP may be sufficient to guarantee membrane integrity over 90 min of ischaemia and so diminish its harmful effects on the myocardium.

Adenosine Triphosphate↗
PubMed1981

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↗
PubMed1980

Changes in myocardial oxygen consumption 45 minutes after experimental coronary occlusion do not alter infarct size.

The influence of myocardial oxygen consumption (MVO2) at the moment of coronary occlusion on the size of the ensuing infarct was investigated in two groups of anaesthetised dogs. In one group (n = 9) coronary occlusion was produced at a high MVO2, estimated to be 14.6 +/- 2.1 cm3 O2 X min-1 X 100g-1 which was changed midway during the occlusion period of 90 min to a low MVO2 estimated to be 6.7 +/- 1.6. In the second group (n = 9) the MVO2, was elevated after 45 min an estimate of 5.1 +/- 0.9 to one of 13.2 +/- 3.7 cm3 X min-1 X 100g-1. In this way the MVO2 averaged over the entire 90 min occlusion period was equal in both groups. Infarct size expressed as a percentage of perfusion area was 68 +/- 28% in group 1 and 32 +/- 30% in group 2 (P less than 0.025). The mass of the perfusion areas did not differ significantly between the groups. Haemodynamics changes were similar in both groups except for a higher rate in group 1 in the period with low MVO2 (109 vs 66 per min, P less than 0.001). Collateral flow was not different between the two groups 45 min after occlusion. It is concluded that the MOV2 at the moment of occlusion significantly influences infarct size. Drastic changes of MVO2 induced at 45 min (ie at half time of the occlusion period of 90 min) had no measurable effect on infarct size.

Animals↗