Cardiac Hypoxia Research Articles

Creatine in density-fractionated red cells, a useful indicator of erythropoietic dynamics and of hypoxia past and present.

Creatine in density-fractionated red cells is not only a useful criterion of cell age but also an excellent indicator of erythropoietic dynamics particularly under the influence of present and past hypoxia. This is documented on patients with cardiac hypoxia. A histogram is proposed which permits the simultaneous evaluation of four parameters: (1) the creatine concentration of each separate fraction, (2) the absolute density of a given cell fraction, (3) the percentage distribution of cells over the whole gradient and within the different fractions and (4) the general position of the red cell population with respect to its median density, which serves to characterize the overall age of a red cell population. Creatine histograms on fractionated red cells are shown to be useful aids for diagnosis and prognosis in hypoxic clinical states. They may also give retrograde information on past stimulation of erythropoiesis.

Evidence from bioassay studies indicating a role for adenosine in cardiac ischemic and hypoxic dilation in the dog.

Previous studies using bioassay demonstrated the presence of a vasoactive substance or substances in coronary sinus blood during myocardial reactive hyperemia which had, on bioassay, characteristics of adenosine and/or AMP. In the present studies, specific blockers were applied to an improved bioassay system to define more precisely the nature of the substance or substances and to determine whether it also appears during local cardiac hypoxia. In the anesthetized dog, coronary sinus blood was bioassayed in an isolated autologous kidney during reactive and hypoxic dilation. During reactive dilation, the bioassay kidney responded with a large resistance increase which was blocked by theophylline and adenosine deaminase and converted to a decrease by adenosine autoblockade. The same was true for hypoxic dilation, except in this instance, only adenosine deaminase reduced the response (40%). Theophylline and adenosine autoblockade eliminated responses of the bioassay organ to both exogenous adenosine and exogenous AMP, but adenosine deaminase was specific for adenosine. These results confirm that one or more vasoactive substances appear in sinus blood in vasoactive quantities during cardiac reactive dilation, and that the peak concentration correlates roughly with the peak flow. In addition, they show that this also is the case for hypoxic dilation. More importantly, they demonstrate that the substance almost certainly is adenosine in the case of reactive dilation, and that increased adenosine levels also are present during hypoxic dilation, but in addition, suggest that AMP sometimes appears in coronary sinus blood during severe cardiac hypoxia in the dog heart.

Metabolic responses to cardiac hypoxia. Increased production of succinate by rabbit papillary muscles.

In oxygen-deprived heart muscle tissue, alanine levels increase, whereas levels of glutamate and aspartate decline, and it is therefore postulated that free tissue amino acids participate in the metabolic response to cardiac hypoxia. Succinate is a hypothetical end product of anaerobic metabolism of glutamate and aspartate. To test this hypothesis in vitro isolated right ventricular papillary muscles from rabbits were individually incubated under oxygenated and hypoxic conditions. Lack of oxygen significantly augmented succinate, lactate, and alanine production, while levels of glutamate fell. Increased succinate production also was seen when various metabolic precursors were present in the oxygenated incubation medium. In hypoxic muscles, succinate production could be enhanced further when these precursors were present. The aminotransferase inhibitor, aminooxyacetate, reduced succinate production by hypoxic papillary muscles. This finding demonstrated a close relationship between transamination of amino acids and succinate production. In addition, it is suggested that anaerobic metabolism of the amino acids glutamate and aspartate, anaerobic glycolysis, and alanine production are quantitatively related. Moreover, the two reactions responsible for succinate production during hypoxia, 2-oxoglutarate dehydrogenase and fumarate reductase, are in oxidation-reduction balance and lead to substrate level phosphorylation in the citric acid cycle. Anaerobic mitochondrial metabolism, resulting in increased synthesis of succinate, must be considered when one estimates the energy production by oxygen-deprived heart muscle.

Postoperative arrhythmias in open-heart surgery, A study on fifty cases.

50 consecutive patients undergone open heart surgery were analyzed regarding postoperative arrhythmias in the first postoperative 3 days. Disturbances of rhythm occurred in each case of our group, serious or not serious (100%). Ventricular premature beats were the most frequent type of arrhythmia in the first and second postoperative days (80%). Two cases expired postoperatively. In one of them complete atrioventricular block developed after double valvular replacements (mitral and tricuspid). The other died of low cardiac output syndrome. Etiology of the arrhythmias after open heart surgery is not clear in the absence of electrolyte and metabolic disturbances, digitalis intoxication and surgical trauma to the conduction system and coronary arteries. Low cardiac output syndrome, hypotension and hypoxia can also be blamed in the formation of these arrhythmias. Other factors such as the prolongation of anoxic arrest, irritation of the ventricular septum by valvular prostheses, cardiac irritation by thoracic tubes, psychologic trauma, halothane anesthesia and coronary arterial disease in the old age group may be the possible predisposing factors in these patients.

Catabolism of adenine nucleotides by the isolated perfused rat heart.

SummaryATP and 5′-AMP were extensively degraded to adenosine and inosine during a single passage through rat hearts perfused in an open-flow system. It is suggested that enzymes which convert adenine nucleotides to adenosine exist within, or on, coronary vascular cells. Whether these enzymes contribute to the formation of adenosine during cardiac hypoxia is unknown.

Electrocardiographic changes during exposure to high altitude

Serial electrocardiograms were obtained in 22 sea level residents and 20 Denver residents while at altitudes of 11,400 or 14,110 feet for four to five weeks. Significant QRS changes were noted in the groups at each high altitude; however, only minimal changes occurred in the Denver subjects at 11,400 feet. Pertinent findings include transient increases in heart rate, decreases in QRS amplitude, and T wave inversion; rightward and posterior shifts in QRS axis were progressive and prolonged. The variables of daily controlled exercise, depth of inspiration, and speed of ascent did not significantly influence the electrocardiographic findings.It is suggested that changes in QRS amplitude and T waves at altitude are transient effects of cardiac hypoxia, while prolonged shifts of the QRS axis may represent early stages of myocardial hypertrophy and are secondary to changes in pulmonary perfusion rather than ventilation.

Stimulation of the coronary collateral circulation by lidoflazine (R 7904).

Lidoflazine, a new and very longacting coronary vasodilator was given to 18 dogs with a chronically developing stenosis and occlusion of the circumflex coronary artery for 4 and 6 weeks respectively. 18 other dogs with chronically developing stenoses leading to occlusion of the circumflex artery were used as controls. Lidoflazine in a dosis of 20 mg/kg/day increased the speed of development of the collateral circulation and prohibited symptoms of permanent cardiac hypoxia. Permanent myocardial hypoxia, caused by a higher degree of physical activity in a group of “freely exercising” dogs produced the same favorable effects on the canine coronary collateral circulation.

Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow.

Experiments were performed on isolated cat hearts perfused with Tyrode's solution and intact hearts of open-chest dogs. Cardiac hypoxia resulted in a decrease in coronary vascular resistance and a release of significant amounts of inosine and hypoxanthine from the myocardium. From 3 to 27 times more inosine and hypoxanthine were released from the heart during myocardial hypoxia than were required to double the coronary blood flow when infused as adenosine into the left coronary artery. Based on the assumption that with hypoxia the nucleotide derivatives leave the myocardial cell as adenosine, an hypothesis is proposed for the metabolic regulation of coronary blood flow.

Pseudoinfarction Pattern of the QRS Complex in Experimental Cardiac Hypoxia Induced by Nor adrenalin

Pseudoinfarction Pattern of the QRS Complex in Experimental Cardiac Hypoxia Induced by Nor adrenalin

THE EFFECTS OF ADRENALINE AND NORADRENALINE ON THE METABOLISM AND PERFORMANCE OF THE ISOLATED DOG HEART

In 16 dog heart-lung preparations modified to permit a more accurate measurement of coronary flow, adrenaline or noradrenaline was infused at a rate of 4 mug. base/min. After a 30-min. pause during which the increased oxygen consumption and heart rate, but not the coronary flow, returned to pre-infusion levels, the other sympathomimetic amine was infused for the same length of time. It was found that, mole per mole, noradrenaline is as effective, and probably more so, than adrenaline in raising the oxygen consumption of the heart-lung preparation. The positive chronotropic and coronary dilating action of both amines appear to be equal. It was observed that in any one experiment the second dose of the sympathomimetic amine was slightly more effective than the first dose in raising the oxygen consumption. The level of high-energy phosphorus compounds does not change after adrenaline or noradrenaline administration even at the time when the oxygen consumption rises to as much as 200%. During this period there are no signs of cardiac hypoxia, as can be judged by the good oxygen saturation of coronary venous blood. Single doses of 5 mug. adrenaline or noradrenaline have a consistent positive inotropic effect that lasts about 15 min. when tested on a failing heart. In 12 experiments on non-failing modified heart-lung preparations, a single dose of 5 mug. adrenaline fails to cause a measurable increase in oxygen consumption after 1, 3, 6, or 11 min. in spite of a mild positive chronotropic action. The significance of these findings is discussed and the suggestion made that, when noradrenaline infusions are effective in treating cardiogenic shock in man, part of this effect may be due to its positive inotropic action, thus correcting an element of heart failure that might exist.

Occurrence of a cardio-active principle in spleen.

THE work of Rein1 and Pinotti2 showed that the liver can release a substance into the circulation which is capable of improving the efficiency of the heart in a manner which could not be explained solely on haemodynamic grounds. These two authors believed that the liver material acted by improving the energy metabolism of the heart, leading to greater economy of cardiac work. Later work reported by Rein3,4 indicated that the stimulus for the release of the active liver principle was cardiac hypoxia, which caused release of a material from the spleen into the blood stream. This material was transported to the liver, where it served as stimulus for the release of the active liver principle. Rein's work has shown that the materials involved in the reaction must be of a hormonal nature. In 1952, Green5 described an extract from the non-saponifiable components of ox liver which exerted a positive inotropic action on the isolated papillary muscle of the cat. This work has been confirmed here, and an examination has been made of extracts of spleen to determine whether any cardioactive material is present in this organ.

Coronary Blood Flow in Hypothermia

Hypothermia as a valuable adjunct to intracardiac surgery has had two limiting factors which have interfered with its widespread acceptance. The relative frequency of ventricular fibrillation which may be irreversible and the short interval of safe blood-flow stasis have been the chief disadvantages observed in attempts to perform intracardiac surgery under hypothermia. The ventricular chambers are not accessible in the cold state, since ventriculotomy causes a very high incidence of fibrillation. The cause of fibrillation is being vigorously studied in many clinics. Swan and his co-workers 8 have investigated the metabolic and electrolyte changes occurring at lowered temperature. Lange, Weiner, and Gold 5 found electrocardiographic changes in hypothermia suggestive of cardiac hypoxia. Penrod, 6 on the other hand, believed that oxygen utilization of the heart was normal at 20C, since he found no change in coronary arteriovenous oxygen differences from those in the normothermic animal. Coronary flow was not measured