Hypoxic Myocardium

In a murine model of myocardial infarction and remodelling created by the left anterior descending 

Hypoxia (10% Oj for 3 weeks) per se induced a rise in hexokinase (EC 2.7.1.1) activity in left and right ventricles and septum of the rat heart and a fall of hydroxyacyl Co-A dehydrogenase (EC 1.1.1.35) activity in both myocardial ventricles (Da-NESHRAD et al. 2000). The respiratory rate and the citrate synthase (EC 4.1.3.7) activities were unaffected by hypoxia. 

Heart muscle cell cultures from 3-days old rats at 40 mm Hg p02 during the first 24 h showed some slightly swollen mitochondrial cristae (Auclair et al. 1976). At 48 h, however, all mitochondria were 

After breathing 5 % O2 for 20 min, reoxygenation for 5 h caused an increase in volume densities of sarcoplasmic reticulum, T-tubuli and mitochondria more intensely in young rats, and of lipid, vacuoles, mitochondrial destruction and average volume prevailing in senescent animals (Welt et al. 2000). 

Myocardial stunning , a reversible contractile failure often found in ischaemic cardiomyopathy is associated with selective degradation of troponin 1, resulting in a truncated molecule that shows considerably reduced calcium sensitivity. It was postulated that intracellular calcium overload due to severe ischaemia could activate the calcium-dependent protease calpain 1, which in turn would cleave troponin I (Gao etal. 1996). Klainguti etal. (2000) have shown that myocardial endo-thelin-1 is increased after 20 min of ischaemia and have suggested that endothelin-1 might play a role as an inducer of apoptosis. 

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Figure 22.17 Summary of mechanisms to maintain the ATP/ADP concentration ratio in hypoxic myocardium. A decrease in the ATP/ADP concentration ratio increases the concentrations of AMP and phosphate, which stimulate conversion of glycogen/ glucose to lactic acid and hence ATP generation from glycolysis. The changes also increase the activity of AMP deaminase, which increases the formation and hence the concentration of adenosine. The latter has two major effects, (i) It relaxes smooth muscle in the arterioles, which results in vasodilation that provides more oxygen for aerobic ATP generation (oxidative phosphorylation). (ii) It results in decreased work by the heart (i.e. decrease in contractile activity), (mechanisms given in the text) which decreases ATP utilisation.

Hypoxic myocardium of rats in experim. aortic stenosis Molbert (1968)... 

It may produce tachypnoea and bradycardia and sensitizes the myocardium to adrenaline and cardiac arrhythmias can occur probably due to hypoxic release of adrenaline. 

As for the cardiovascular system, the cardioprotective effects of selective H3-receptor agonists, demonstrated in models of protracted myocardial ischemia (Imamura et al., 1994, 1995, 1996a Hatta et al., 1996, 1997), could be predictive of beneficial effects in coronaropatic patients. Hence, the attenuation of carrier-mediated noradrenaline release in hypoxic and/or ischemic myocardium by H3-agonists would limit the sympathetic overactivity and the associated incidence of ventricular arrhythmias and angina, as well as the increase of metabolic demand by the myocardium, thus preventing further damage and cardiac failure. 

Sawa, Y., Ichikawa, H., Kagisaki, K., Ohata, T., and Matsuda, H., Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium. J. Thorac. Cardiovasc. Surg. 116, 511-517 (1998). 

Autopsy revealed early hypoxic changes in the myocardium (Ellis et al. 1982). In another case, cardiac output, heart rate,... 

Preliminary studies321 in isolated perfused rabbits hearts following 15 minutes of infusion of [18F]-330 showed greater accumulation of [18F]-330 in ischemic (62 + 7%) or hypoxic hearts (61 11%) when compared to control hearts (25 5%). 330 is therefore a promising tracer for delineation of ischemic but viable myocardium. 

J. Neckar, I. Markova, F. Novak, O. Novakova, O. Szarszoi, B. Ostadal and F. Kolar, Increased expression and altered subcellular distribution of PKC isoform delta in chronically hypoxic rat myocardium involvement in cardioprotection, Am. J. Physiol. 288(4), H1566-72 (2004)... 

Since the beginning of the 1990s, much effort has been devoted to develop " " " J c radiopharmaceuticals for the detection of hypoxic tissue in the myocardium, brain. 

Halothane (Fluothane) Mechanism unclear. Induces rapid, comfortable anesthesia and skeletal muscle relaxation. i cardiac output, mild T of systemic vascular resistance, typically no effect on heart rate, 1 right atrial pressure, moderate depression of myocardial function, most likely to sensitize myocardium to catecholamines and i baroreceptor reflex. t ventilation control (T tidal volume, >1 rate of breathing, i response to CCfe and hypoxia), bronchodilation (mostpotent), No effect on hypoxic pulmonary vasoconstrictor response, depression of ciliary function and mucous clearance. 

Isoflurane (Forane) Least likely to T right atrial pressure, depress myocardial function, or sensitize myocardium to catecholamines. Greatly i systemic vascular resistance. Marked T heart rate Least potent suppressor of ventilation control and bronchodilation. Marked suppression of hypoxic pulmonary vasoconstrictor response, little effect on secretions. 

Cardiovascular effects Cardiopulmraiary arrest, early hypoxic changes in the myocardium, cardiogcmic shock, cmnplicated by pancreatitis and gut mucosal necrosis and hemorrhage, hypotension, ventricular arrhythmias, sevcae respiratory distress, and metabolic acidosis... 

HR [min ] Coronary flow [ml/min 100 gm] Venous PO2 (PVO,) Oxygen extraction xmHg] [%] Hypoxic part of myocardium... 

The effect of anemia on the coronary flow was studied here (Table 3), by comparing the two values of abnormal hemoglobin concentrations, Hb = 0.07 gm/ml and Hb = 0.04 gm/ml, to the normal value of 0.15 gm/ml. Anemia is shown here to be associated with increased coronary flow, increased oxygen extraction and a decrease in the oxygen tension in the coronary venous blood. (Jan et ai, 1977). It is shown by the model that at hemoglobin values of 0.07 gr/ml and a heart rate of 120 cycles per minute the myocardium is not hypoxic throughout. However, when Hb = 0.04gm/ml, similar heart rate is associated... 

Kammermeier H, Schmidt R, Jungling E (1982) Free energy change of ATP hydrolysis a causal factor of early hypoxic failure of the myocardium. J Molec Cell Cardiol 14 267-277... 

Ischemic injury results in a marked decrease in the plasmalogen content of biomembranes. Thus in rabbit myocardium, microsomal plasmalogen-selective PLA activity is markedly increased by 10-fold during ischemic injury (Hazen et al, 1991). A marked stimulation of plasmalogen-selective PLAj also occurs during hypoxic injury to rabbit proximal tubules (Portilla et... 

The main effect of hawthorn is on the cardiovascular system. Pharmacological studies report enhanced coronary blood flow and myocardial perfusion improvement of cardiac muscle contractility increased left ventrical output velocity lowering of blood pressure " an antiarrhythmic effect increased myocardium tolerance to oxygen deprivation under hypoxic conditions cardioprotective effect against myocardial infarc-tion and stimulation of revascularization after myocardial ischemia (escop 1) Various clinical studies reveal efficacy in congestive heart failure increased cardiac performance decrease in peripheral vascular... 

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