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Biomedical subjects

W Schaper

Publications and source records attributed to W Schaper.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

The influence of reperfusin on infarct size after experimental coronary artery occlusion.

Reperfusion following various intervals of coronary occlusion has produced conflicting results: increase in infarct size, especially with hemorrhage into the tissue, was reported as well as salvage of ischemic myocardium. To examine the problem and for the validation of our own method for infarct size measurement, which depends to a certain degree on reperfusion, we occluded two coronary arteries of the same heart in each of 12 open-chest dogs. One artery was reperfused, the other not. Comparable conditions for both occlusions were warranted by selection of small-to-medium sized arteries of equal size and by maintaining of constant MVO2. Reperfused and non-reperfused myocardium did not differ with regard to infarct size, neither after a three-hour nor after a six-hour occlusion. Reperfusion always led to hemorrhagic infarction when performed after six-hour occlusion, while nonreperfused infarctions showed no hemorrhage. Hemorrhage infarcts were not larger as compared to the non-hemorrhagic infarct in the same heart.

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PubMedDate not supplied

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog.

The effects of 3 different doses (0.02, 0.1, 0.5 mg/kg/h) of dipyridamole on myocardial infarct size were evaluated in pentobarbital anesthetized open-chest dogs following sequential coronary occlusion of two medium sized coronary arteries in the same heart. The first coronary occlusion produced a control infarct, the other a test infarct under the influence of the drug. Dipyridamole infusion was started 10 min before the second occlusion at a rate of 0.02 (group A, n = 9), 0.1 (group B, n = 10) or 0.5 (group C, n = 9) mg/kg/h respectively and continued to the end of reperfusion (90 min). Biopsy samples were obtained at the end of each occlusion period and at the end of the second reflow period. Infarct size was determined using post mortem angiography and pNBT staining. Control and treated infarct sizes, expressed as a percentage of the perfusion area, were 21.9 +/- 5.4% vs. 25.2 +/- 7.7% in group A (n = 9), 21.8 +/- 7.3% vs. 18.3 +/- 5.2% in group B (n = 9), and 22.3 +/- 7.7% vs. 16.2 +/- 4.8% in group C (n = 8). There were no significant differences between control and treated infarct sizes in the 3 groups. After 90 min coronary occlusion tissue adenosine contents in the ischemic myocardium were significantly higher (42 +/- 7 nmol/gww in group C and 40 +/- 5 nmol/gww in group B) than those in the nonischemic myocardium, and dipyridamole enhanced these levels (395 +/- 6 nmol/gww in group C: p less than 0.01, 55 +/- 10 nmol/gww in group B). Dipyridamole did not affect the tissue inosine levels in the ischemic myocardium after 90 min coronary occlusion. ATP and creatine phosphate levels were not affected by dipyridamole during ischemia or during reflow. The accumulated adenosine was not phosphorylated to AMP and on to ATP upon reperfusion.

Adenosine↗
PubMedDate not supplied

The effect of beta-adrenergic blockade on infarct size following experimental coronary occlusion.

The effect of Pindolol on myocardial infarct size was studied in 10 open chest dogs. In each animal a sequential occlusion and reperfusion of 2 medium-sized branches of the left coronary artery was performed in the same heart. After occlusion and reperfusion of the control artery the initial dose of Pindolol (0.25 mg/kg body weight) was administered. Thereafter the test artery was occluded, followed by a maintenance dose of Pindolol (0.3 mg/kg body weight). The drug caused a significant decrease in LVP and LV-dp/dt but no change in heart rate. MVO2 also decreased significantly. Regional myocardial blood flow was measured with the tracer microsphere method. Collateral flow in the perfusion area of the control artery was 11.2 +/- 5.9% and in the area of the test artery 10.0 +/- 4.4% of normal. No change in the endo/epi ratio as a result of treatment was observed. The area of infarction (p-nitroblue tetrazolium-reaction) was divided by the area of perfusion (angiography). Infarct size, expressed as the percentage of the perfusion area, was 48.2 +/- 22.2% in the region of the control artery and 43.0 +/- 23.9% in the region of the test artery. The difference was statistically not significant.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Myocardial protection by collateral vessels during experimental coronary ligation: a prospective study in a canine two-infarction model.

Previous work of this laboratory has shown that collateral flow can be increased over six weeks by a subcritical external constriction of the circumflex artery causing a 50 +/- 10% reduction of postocclusive reactive hyperemia. To investigate collateral function in acute myocardial infarction, the model was used to ligate two distant coronary branches on the ventricle simultaneously in order to compare in 8 dogs infarct size and perfusion area of the ligated vessels in control and collateralized sections. The acute collateral flow measured 7.2 +/- 2.5 ml/100 g/min-1 and increased to 17.3 +/- 6.7 (p less than 0.001) over 6 weeks. Separate analysis revealed a predominant increase of collateral flow in the epicardial layers 23.1 +/- 7.5 (p less than 0.01) versus 6.9 +/- 2.8 (p less than 0.01) in the subendocardium. Infarct size in the control area was 52.0 +/- 14.7% of the perfusion area, in the collateralized zone 19.0 +/- 14.2% (p less than 0.001). Infarct size expressed as per cent of perfusion area and collateral flow in the area at risk expressed as per cent of flow of normal sections correlated: (r = 0.76; p less than 0.05). Therefore, infarct size after a 6 hour coronary occlusion can be considered a function of the collateral flow over normal perfusion ratio. Localized induction of collaterals in this model caused a significant reduction of infarct size in relation to the perfusion area at risk.

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PubMedDate not supplied

Measurement of radioactive tracer microsphere blood flow with NaI (T1)-and Ge-well type detectors.

An intrinsic Ge-well type detector was applied for the detection of gamma rays from labeled tracer microspheres. The high energy resolution and the large peak-to-Compton ratio of this spectrometer ensures the application of all available differently labeled tracer microspheres in one experiment. The superior energy resolution of the Ge-detector was documented with the separated photopeak regions of 103-Ru and 85-Sr-labeled tracer microspheres, which result in a single photopeak when an NaI(T1) detector is used. The Ge-well type detector was compared with an NaI(T1) spectrometer by counting samples of cardiac muscle in either spectrometer systems. Regression analysis between both spectrometer systems demonstrate identical flow values in these samples for 5 differently labeled tracer microspheres which were administered in 5 dogs. The high sensitivity of the Ge-well-type detector together with a suitable technique for sampling of myocardial tissue accomplishes a high spatial resolution of myocardial perfusion for all available differently labeled tracer microspheres.

Animals↗
PubMedDate not supplied

Loss of canine myocardial nicotinamide adenine dinucleotides determines the transition from reversible to irreversible ischemic damage of myocardial cells.

We investigated if the loss of nicotinamide coenzymes in ischemic-infarcted myocardium may be responsible for the transition from reversibly ischemic to irreversibly infarcted cell damage. The LAD was occluded in 6 dogs for 4 h. Transmural needle biopsies were taken from he ischemic-infarcted region after 1/2, 1, 11/2, 2, and 4 h of ischemia and further divided into subepicardial and subendocardial halves. At each time interval the concentration of the nicotinamide coenzymes NAD, NADH, and NADPH were measured, and the degree of cellular injury was evaluated by electron microscopy. The glycohydrolase activity (EC 3.2.2.5), the enzyme which splits NAD, was determined in brain, myocardium, kidney, and skeletal muscle of 4 rats. Total NAD, the sum of NAD and NADH, started to decrease significantly in the ischemic subendocardium 1 h after onset of ischemia. Degradation of NADPH occurred later. Loss ot total NAD was about 60-70% when electron microscopy diagnosed irreversible cell injury. The glycohydrolase activity was the highest in brain followed by myocardium, kidney, and skeletal muscle, reflecting the different tolerances of these tissues towards ischemia. The key mechanism for ischemic injury seems to be the tissue acidosis which activates the glycohydrolase leading to a loss of the vital coenzymes.

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PubMedDate not supplied

Experimental myocardial infarction in a closed-chest canine model. Observations of temporal and spatial evolution over 24 hours.

Myocardial infarction was induced in 7 mongrel dogs by transfemoral intraluminal occlusion of the left anterior descending coronary artery. Perfusion area at risk was determined by post-mortem coronarography and infarct size by macrohistological staining with para-nitrophenoltetrazolium. Regional flow was determined by injection of radioactive microspheres 0.2 hours, 12 hours, and 24 hours post occlusion. Infarct size as determined by planimetry of post-mortem angiograms and macrohistological stains at identical magnification revealed 74.5 +/- 12.1% infarcted tissue of the perfusion area at risk. The flow of the necrotic tissue was below 13 Ml/100 g min without exception, indicating a threshold perfusion for maintenance of myocardial viability. Accordingly, a flow of less than or equal to 10 ml/100 g min identified 93% of the entire infarcted myocardium, resulting in 71 +/0 20% as compared to the perfusion area at risk. Based on the good agreement of macrohistological and flow data, the evolution of myocardial injury was determined by flow measurements. The results indicated a different progression of the borders of critical flow in the subendocardial and subepicardial layers, whereas in the subendocardium 85% of the tissue at risk was identified by the critical flow at 0.2 hours and 97% at 12 hours, the subepicardial flow changed at a different pace: only 53% showed subcritical perfusion at 0.2 hours, 61% at 12 hours with a final increase of 39% from 12 to 24 hours.

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PubMedDate not supplied

Effect of myocardial oxygen consumption on infarct size in experimental coronary artery occlusion.

The influence of myocardial oxygen consumption (MVO2) at the moment of coronary occlusion on the size of the ensuing necrosis was investigated in 12 anaesthetised dogs. A two-infarction model was used with a sequential occlusion of two distant coronary branches in the same heart, however under different levels of MVO2. One group of occlusions was produced at a high MVO2 of 21.6 +/- 3.0 ml O2 . min-1 . 100 g-1. This group was compared with a second in which necrosis proceeded at a low MVO2 estimated to be 5.9 +/- 1.5 ml O2 . min-1 . 100 g-1 averaged over a 90-min occlusion period. Infarct size expressed as percentage of perfusion area was 43 +/- 28% in group 1 and 11 +/- 11% in group 2 (p less than 0.005). The mass of the perfusion area was equal in both groups (17 +/- 4 g, 19 +/- 6 g). The amount of myocardial necrosis, which after a 90-min occlusion depends on the acute collateral blood flow, was in every case greater under high MVO2. Thus a low MVO2 at the moment of occlusion can postpone myocardial necrosis.

Animals↗
PubMedDate not supplied

Ineffectiveness of methylprednisolone to reduce infarct size in experimental coronary occlusion.

Two medium-sized branches of the left coronary artery were prepared in each of 10 anesthetized open chest dogs for later occlusion. The first artery was occluded during 90 minutes and reperfused thereafter. This occlusion produced the control infarct. Methylprednisolone (50 mg/kg i.v.) was injected and the second artery was occluded also for 90 minutes and reperfused thereafter. Both infarcts were made visible by staining left ventricular rings with p-nitrobluetetrazolium. Infarct size was compared with the size of the perfusion area, which we obtained from the postmortem angiogram. Both infarcts were equal in size and comprised 50% of the area of perfusion of the occluded artery. Methylprednisolone in a single high dose given prophylactically did not influence infarct size nor any of the measured parameters.

Animals↗
PubMedDate not supplied

Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium.

We investigated whether the postischemic acceleration of adenosine triphosphate (ATP) synthesis by means of precursor infusion is beneficial for the contractile function of reperfused myocardium. A coronary artery was occluded for 45 min in 21 dogs to produce a marked but reversible ischemia. During the following 3 hours of reperfusion either adenosine (n = 6) or AICAR (5-amino-imidazole-4-carboxamide-riboside) (n = 6) was infused intracoronarily by a small transfemoral catheter positioned in the LAD. ATP repletion by adenosine was nearly 50% of the deficit caused by the previous ischemia, the effect of AICAR on steady-state tissue ATP concentration was insignificant. Regional systolic function of these both groups was compared to that of a control group (n = 9) receiving only a saline infusion. We measured the regional function by subendocardially implanted ultrasound transducers using the transit time method. All three groups showed a reduction to about 25% of the initial segment shortening at the end of ischemia, followed by a quick recovery to half of the preocclusion segment shortening after reopening of the vessel. No further changes were observed in the control series during the 3 hours of reperfusion (50 +/- 10% SE segment shortening at the end). With adenosine infusion - in spite of the resulting considerable ATP elevation - no significant change of segmental contractile function occurred (44 +/- 5% SE segment shortening). Only the AICAR treated group differed from control. It produced a continuous deterioration during reflow resulting in a holosystolic bulging of -20% +/- 10% SE at the end of 3 hours of reperfusion. Our results show that there is no correlation between different ATP tissue levels achieved by adenosine infusion and systolic function in reperfused myocardium after regional reversible ischemia. We hypothesize that reperfusion dyskinesia is caused by a failure of energy utilisation rather than of energy supply.

Adenosine↗
PubMedDate not supplied

Microvascular and collateral adaptation in swine hearts following progressive coronary artery stenosis.

We chronically implanted hygroscopic occluders around the left circumflex coronary artery in 49 anesthetized young male domestic pigs and we studied the development of a collateral circulation at 4, 8, 12, and 26 weeks after implantation. At these time intervals groups of animals were again anesthetized, the hearts were explanted and perfused in Langendorff-fashion with leucocyte-filtered pig blood. Maximal coronary vasodilation was induced with adenosine and global (electromagnetic), and regional (tracer microspheres) blood flow was measured at 40, 60, 80, and 100 mm Hg of perfusion pressure. At 4 weeks after occluder implantation maximal left circumflex collateral blood flow was about 20% of normal maximal flow. Collateral flow rose to 60% of maximal normal flow between 4 and 8 weeks and did not improve further with longer time intervals. In contrast to the canine heart numerous small vessels develop in response to ischemia in the pig heart. These vessels develop throughout the entire risk region with a slight preference for the subendocardium. They appear on tomographic angiograms as a dense "blush". The study of the relationship between peripheral coronary pressure vs collateral flow showed a relationship much steeper than that of normal maximal flow vs aortic perfusion pressure which indicates that the minimal resistance of the risk region was decreased as part of the mechanism to ensure adequate blood supply in a situation of progressive coronary narrowing.

Adaptation, Physiological↗
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Mitochondrial damage during myocardial ischemia.

The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in whole tissue. Adenine nucleotide translocator (ANT) was severely inhibited and seemed to be a sensitive indicator of a lesion of the inner mitochondrial membrane. Postischemic reperfusion led to a slight loss of adenine and pyridine nucleotides from the reversibly damaged subepicardium and to an enormous loss from the irreversibly damaged subendocardium. The washout of nucleotides from irreversibly damaged areas caused the negative para-Nitro Blue Tetrazolium ( pNBT ) staining of the infarcted tissue. Diagnosis of cell death with pNBT failed after the occlusion period without reflow because pyridine, although lost from the mitochondria, was still present in the tissue. In reversibly injured areas, mitochondrial function and ultrastructure were restored after reperfusion, although a significant nucleotide loss was found in the tissue. These studies suggest that mitochondrial ultrastructure and function may play a key role in cellular viability during recovery from ischemia.

Adenine Nucleotides↗
PubMedDate not supplied

Mechanical activity of isolated canine coronary arteries after coronary occlusion.

Collateral vessels from dogs showed good mechanical responses, with well-developed inhibitory responses, for example to noradrenaline. Endogenous inhibitory processes, which resulted in a low spontaneous basal tone, were also well-developed in most tissues. However, signs of hyperactivity were observed in some cases - and this might be the most interesting result. This hyperactivity was characterized by a strong phasic spontaneous activity. This might be an abnormality associated with the rapid proliferation of smooth muscle cells in collateral vessels. It is quite possible that such states of hyperactivity may play a role in human pathology, Producing coronary spasm and leading to angina or infarction, perhaps even in hearts with well developed collaterals.

Animals↗
PubMedDate not supplied

Is malondialdehyde a marker of the effect of oxygen free radicals in rat heart tissue?

We tested the effect of exogenous purine derived free radicals and H2O2 vs ischemia and reperfusion on the thiobarbituric-acid (TBA)-reactive material and malondialdehyde (MDA) formation in isolated rat hearts using the thiobarbituric acid test and high performance lipid chromatography (HPLC). We could not detect increased thiobarbituric-acid-reactive material or MDA production during 6 mM H2O2 infusion, during free radical generation by purine-derived free radicals, or using ischemia and reperfusion. Increased thiobarbituric-acid-reactive material and MDA tissue levels were detected only during infusion of 12 mM H2O2 (p less than 0.001). We conclude that the generally used thiobarbituric acid assay for MDA is susceptible to artifacts and unsuited as an indirect measure for low-to-medium-levels of oxygen free radicals. Using HPLC assay, which accurately measures MDA, no evidence was found that MDA is a primary and direct lipid peroxidation product of exogenous or endogenous reactive oxygen species.

Animals↗