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Biomedical subjects

S M Humphrey

Publications and source records attributed to S M Humphrey.

At least 37 records · Page 2Linked to original sources
PubMed1984

Adenine pool catabolism in the ischemic, the calcium-depleted ischemic, and the substrate free anoxic isolated rat heart: relationship to contracture development.

Metabolic changes in the myocardial adenine and hypoxanthine pools of isolated rat hearts subjected to global ischemia, hypocalcemic global ischemia, and global substrate-free anoxia were compared. At timed intervals between 0 and 60 min separate aliquots of extracts of the ventricles were used to determine either tissue pH, or the components of the adenine pool and their catabolites by reverse phase high performance liquid chromatography (HPLC). The coronary perfusate draining from anoxically perfused hearts was collected over perchloric acid, neutralised and chromatographed by HPLC. The development of left ventricular resting tension (contracture) was recorded in the three groups of hearts. After 60 min ischemia the major catabolites, (AMP, inosine and hypoxanthine) comprised 70% of the total pool (11, 7 and 4 mumol/g dry wt, respectively). After the same period of anoxia 50% of the total pool, comprising adenosine, inosine, hypoxanthine and uric acid in approximately equal proportions, was recovered from the coronary perfusate. The major products remaining in the tissue were IMP and, to a lesser extent AMP (8 and 5 mumol/g dry wt, respectively). Left ventricular contracture developed at different rates in the three groups of hearts but always correlated closely with the maximum rate of adenine pool catabolism. The loss of components from the tissue and the divergence in pathway from adenosine to IMP production which occurs during anoxic perfusion should possibly be considered when assessing the biochemical events occurring in regionally ischemic heart muscle with significant residual flow.

Adenine↗
PubMed1983

Changes in vascular morphology associated with the no-reflow phenomenon in ischaemic myocardium.

To investigate the pathogenesis of the reperfusion defect which develops in ischaemic myocardium, intravascular casts were prepared by injection of methyl methacrylate into the coronary arteries of isolated heparinised rat hearts. Using a scanning electron microscope, the vascular morphology following 60 min of global ischaemia at 37 degrees C was compared to that of non-ischaemic control hearts injected immediately after stopping perfusion with oxygenated Krebs-Henseleit buffer. Complete casts were obtained from control hearts and from all parts of ischaemic hearts except the subendocardial half of the left ventricular wall of ischaemic hearts where the blood vessels were not filled. At the border between the perfused subepicardial and unperfused left subendocardial regions, the resin which filled the radial penetrating arteries and their branches projected from the filled capillary plexus to an extent proportional to their diameter. Intravascular events such as erythrocyte plugging and thrombosis were excluded as causative factors by the use of a cell-free perfusate. Also, there was no morphological evidence that endothelial cell swelling or constriction of any particular population of vessels was involved. The observed pattern of vascular occlusion suggests that, during global ischaemia, blood vessels in the endocardial half of the left ventricular myocardium lose their ability to be reperfused because of extravascular compression.

Animals↗
PubMed1983

Effects of proton release from adenine nucleotide degradation during ischemic necrosis of myocardium in vitro.

The effects of the progressive production of hydrogen ions and inorganic phosphate from adenine nucleotides on the lowering of pH in heart muscle has been investigated in dog myocardium maintained under anoxic conditions in vitro at 37 degrees C. Tissue samples were taken at 15-min intervals for up to 105 min and the following biochemical parameters determined: pH, lactate, Pi, ATP, ADP, AMP, G6P, and PC in selected instances. From these data the net proton changes during prolonged anoxia were calculated, assuming homogeneity of the tissue milieu. Net proton change was negative after 15 min and became increasingly more so throughout the remainder of the experimental period, indicating that adenine nucleotide catabolism in fact has a protective effect against fall in pH. When tissue pH falls to ca. 6.2 (45-60 min anoxia), proton production due to lactic acid is reduced by approximately 16% because of absorption of protons by phosphate and ammonia liberated from the nucleotides.

Adenine Nucleotides↗
PubMed1982

The influence of adenosine on the no-reflow phenomenon in anoxic and ischaemic hearts.

Adenosine and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), separately and in combination, were added to the perfusate of isolated rat hearts which were then subjected to ischaemia or anoxia. The effect of these infusates on the vascular competence of the myocardium subjected to oxygen deprivation of from 15-90 min was compared to control hearts. Vascular competence at selected time intervals was assessed from the distribution of injected. 1% sodium fluorescein in the cut surface of the ventricles. A region of non-perfusion surrounding the left ventricular lumen and involving 25% of the ventricular myocardium developed within 15 min of anoxic perfusion, with little change thereafter. Adenosine had no significant effect on this. The no-reflow phenomenon following ischaemia had similar distribution, but developed more slowly and eventually involved twice as much of the myocardium (59% after 90 min). Surprisingly, pre-treatment with adenosine greatly increased (from 14-46%) the extent of no-reflow after 30 min of ischaemia. Pre-treatment with EHNA caused a slight reduction (59-43%) in its extent but only after 60 min. Thus the no-reflow phenomenon which developed in ischaemic myocardium is unlikely to be due to the reduced vasodilatory action of adenosine.

Adenine↗
PubMed1982

Improved functional recovery of ischemic myocardium by suppression of adenosine catabolism.

Isolated working rat heart preparations were used to ascertain whether the addition of adenosine and prevention of its catabolism could aid in the functional recovery of hearts following global ischemia. Hearts were infused with either 80 micro M EHNA (an adenosine deaminase inhibitor) or 20 micro M adenosine and EHNA in either normal (2.4 mM) or low (0.05 mM) calcium-containing buffer prior to clamping of the aorta for 30 minutes. In one series of hearts, postischemic concentrations (mumoles/gram wet weight) of adenosine triphosphate (ATP), diphosphate (ADP), and monophosphate (AMP), adenosine, inosine, and hypoxanthine were measured; in another series, the recovery of aortic flow rate was used as a measure of functional recovery of ventricular muscle. With normal electrolyte balance, EHNA was unable to protect hearts against ATP loss and ventricular failure. Hearts with EHNA + adenosine recovered 14% of preischemic aortic output and ATP levels were slightly elevated at 0.93 mumole/gm. Those treated with either EHNA or EHNA + adenosine in low-calcium buffer recoverd 100% of their original aortic output. However, EHNA + adenosine maintained considerably higher ATP levels (1.57 mumoles/gm) than did EHNA alone (1.14 mumoles/gm) and was associated with faster initial recovery of aortic output. Thus the prevention of adenosine catabolism was insufficient for adequate ventricular recovery unless the tissue ATP was maintained above about 1.0 mumole/gm. EHNA + adenosine in a 0.05 mM Ca++ infusion solution conserved ATP, markedly improved the functional recovery of hearts, and thus may have a role to play in myocardial preservation during elective cardiac arrest.

Adenine↗
PubMed1981

Changes in the contractile state, fine structure and metabolism of cardiac muscle cells during the development of rigor mortis.

Transmural slices from the left anterior papillary muscle of dog hearts were maintained for 120 min in a moist atmosphere at 37 degrees C. At 15-min intervals tissue samples were taken for estimation of adenosine triphosphate (ATP) and glucose-6-phosphate (G6P) and for electron microscopic examination. At the same time the deformability under standard load of comparable regions of an adjacent slice of tissue was measured. ATP levels fell rapidly during the first 45 to 75 min after excision of the heart. During a subsequent further decline in ATP, the mean deformability of myocardium fell from 30 to 12% indicating the development of rigor mortis. Conversely, G6P levels increased during the first decline in adenosine triphosphate but remained relatively steady thereafter. Whereas many of the myocardial cells fixed after 5 min contracted on contact with glutaraldehyde, all cells examined after 15 to 40 min were relaxed. A progressive increase in the proportion of contracted cells was observed during the rapid increase in myocardial rigidity. During this late contraction the cells showed morphological evidence of irreversible injury. These findings suggest that ischaemic myocytes contract just before actin and myosin become strongly linked to maintain the state of rigor mortis.

Adenosine Triphosphate↗
PubMed1981

The effect of an isovolumic left ventricle on the coronary vascular competence during reflow after global ischemia in the rat heart.

During global ischemia in isolated rat hearts, the development of contracture, due to irreversible myofilament sliding, causes reduction of left ventricle luminal volume. Also, a considerable area of the myocardium cannot be reperfused after 1 hour's global ischemia. The purpose of this study was to reduce myofilament sliding by placing a fluid-filled isovolumic balloon in the left ventricular cavity of isolated rat hearts and assess the extent of reflow, after 60 minutes' ischemia, by perfusion of a 1% fluorescein tracer solution. Light and electron microscopy was used to determine the state of the vasculature and myofibrillar apparatus. In hearts without the left ventricular balloon (control) the ischemia produced a no-reflow zone comprising 45% of the myocardial wall. In contrast, if an isovolumic balloon was in place during the ischemic period, only 6% of the wall was involved. The volume of the capillary bed in the subendocardium of the control hearts was about 60% of that in th isovolumic hearts. In the isovolumic ("isometric") mode, ischemic contracture was associated with more severe myocardial cell injury than in the corresponding control ("isotonic") mode. Our results support the concept that intramyocardial pressure generated by ischemic contracture plays a major role in the production of the no-reflow phenomenon in globally ischemic rat hearts, and indicate that it is the series elastic component of cardiac muscle which imparts the stiffness necessary to prevent reopening of coronary vessels after a severe ischemic insult.

Animals↗
PubMed1978

The calcium paradox: metabolic, electrophysiological, contractile and ultrastructural characteristics in four species.

The effect of transient depletion and repletion of calcium upon the electrophysiological activity, contractile activity, coronary flow, tissue energy metabolism and the cellular leakage of metabolites and creatine kinase has been characterized in the rat heart and now has been compared with the mouse, guinea pig and rabbit heart. The sudden and massive damage (the calcium paradox) which occurred in the rat was observed in all species studied. While fine differences between species were detectable, the basic principles and damaging effects of sudden transmembrane calcium fluxes would appear to be common to all species.

Animals↗