Paul Kezdi

Responses of the ischemic myocardium to allopurinol

Abstract Allopurinol was found to have a profound effect on hemodynamic, ECG, and biochemical changes of experimental myocardial ischemia produced by coronary artery ligation in dogs and sheep. Following acute infarction, intravenously administered Allopurinol caused an increase of myocardial contractility and cardiac output, reversed or prevented electrocardiographic S-T changes of ischemic origin, and exhibited prolonged antiarrhythmic effects. It is suggested that prevention of the irreversible loss of purine base from the cell during hypoxic states is the biochemical action of this drug that results in rapid recovery of the stressed myocardium. The results of the experiments indicated that Allopurinol may be a useful agent for the treatment of coronary insufficiency.

Ebstein's malformation∗: Clinical findings and hemodynamic alterations

Abstract Clinical, electrocardiographic, cardiac catheterization and angiocardiographic findings in Ebsteins malformation of the tricuspid valve were reviewed. Three of our own cases are reported, showing different degrees of the malformation and different degrees of symptoms, from impaired cardiac function, to almost no reduction of cardiac efficiency. Ebsteins malformation may be suspected and diagnosed clinically. However, in some cases the degree of malformation is mild and the findings are less typical clinically. Cardiac catheterization usually leads to the diagnosis. An unusual normalization of the previous right bundle branch block pattern occurred in one of the cases during cardiac catheterization, which lasted for 20 to 25 cardiac cycles and appeared and disappeared without any change in the normal sinus rhythm. The previous delay in the onset of the right ventricular pressures and the broadening and late peak disappeared during the normal conduction. Two possible alternative explanations are offered which might shed some light on the electrical activation and hemodynamics of the right ventricle in Ebsteins malformation. It is possible that the catheter blocked the activation of the atrialized portion of the right ventricle and thus changed the right ventricular hemodynamics. On the other hand, it is possible that aberrant right ventricular conduction mechanism is present in Ebsteins malformation which changed to a shorter and normal intraventricular conduction when interference from the catheter blocked the aberrant pathways. Such aberrant pathways are supported by the occurrence of right ventricular pre-excitation in another case during cardiac catheterization. Angiocardiography in one of the patients showed that in Ebsteins malformation there is a hemodynamically non-functioning part of the right atrium, the atrialized portion of the right ventricle, which is placed between the vigorously contracting right atrium and the functioning small part of the right ventricle.

Reflex inhibitory effects of vagal afferents in experimental myocardial infarction

Abstract In experimental myocardial infarction with hypotension, low output state and shock (produced by injection of 0.2 ml of metallic mercury into the circumflex coronary artery of closed chest anesthetized dogs) serial recordings were made of postganglionic sympathetic and aortic baroreceptor nerve activity in addition to cardiac output, mean blood pressure, electrocardiogram and heart rate. With the decrease in cardiac output and mean blood pressure after injection of mercury, aortic nerve activity decreased as expected but, contrary to expectations, postganglionic sympathetic nerve activity also decreased. It was postulated that this decrease was due to a powerful cardiac vagal afferent reflex that could override the compensatory increase of sympathetic activity usually present with systemic baroreceptor withdrawal. Cutting or blocking the vagus nerves resulted in an immediate increase in sympathetic nerve activity followed by increases in cardiac output, mean systemic blood pressure and aortic nerve activity. Atropine, although it increased heart rate, did not reproduce the effect of vagotomy on sympathetic activity and cardiac output.

Control by the Superior Cervical Ganglion of the State of Contraction and Pulsatile Expansion of the Carotid Sinus Arterial Wall

The state of contraction and resistance to stretch of the arterial wall of the carotid sinus modulates sensitivity of pressoreceptors to intra-arterial pressure. Experiments show that electric stimulation of efferent sympathetic pathways to the carotid sinus leads to blood pressure fall and decrease of the carotid sinus hypertensive reflex. This effect can be prevented by local application of Regitine to the carotid sinus. These experiments suggest that the state of contraction and resistance to stretch of the barosensitive arterial walls is controlled by sympathetic innervation through local release of norepinephrine and/or epinephrine. Disturbances of this innervation could have a role in development of abnormal relaxation and decreased pulsatile expansion of the barosensitive arterial walls, and, thus, in the pathogenesis of hypertension.

RESPIRATORY AND CARDIOVASCULAR FUNCTION IN PATIENTS WITH SEVERE PULMONARY HYPERTENSION.

HEATH and Whitaker 1 applied the term hypertensive pulmonary vascular disease to patients with chronic, severe pulmonary hypertension. They emphasized that this disease is a distinct clinicopathologic entity with uniform clinical features and characteristic morphologic changes of the pulmonary arteries and arterioles irrespective of the etiology of the hypertension. The vascular changes indicate restriction of the pulmonary vascular bed, which may alter pulmonary gas exchange. This study of the respiratory physiology of such patients was undertaken to determine if the uniform clinical picture could in part result from some common, specific pathophysiologic mechanism.

Mitral Ball-Valve Prosthesis Dynamic and Clinical Evaluation

Flow dynamic studies were performed in a mechanical pulse duplicator with Starr-Edwards ball valves. It was shown that the “effective orifice” of the ball valve is less than the measured orifice of the cage of the valve. The orifice is decreased to 83 per cent of the measured orifice in the smaller and to 89 per cent in the larger valves. These measurements corresponded well with the measurements of the “effective orifice” of the valve implanted in patients who were examined by left and right heart catheterization and left ventricularangiocardiograms several months after placement of the valve.The closing regurgitation found in early systole in the mechanical system appears to be negligible in patients. Left ventricular angiograms did not show reflux of dye into the left atrium through the valve cage.The size of the mitral annulus in patients was measured from left ventricular angiograms. The size of the mitral ball valve prosthesis which the mitral annulus will accommodate could be predicted with good accuracy from these measurements.

Mechanism of the carotid sinus in experimental hypertension.

• In recent years interest has been renewed in the role of baroreceptors in hypertension. It was emphasized again by Heymans and Neil that the baroreceptors function not only as regulators, but also as moderators, since they constantly decrease high central sympathetic vasoconstrictor and cardiac accelerator outflow to normal levels. Bemoval of this function by disruption of the buffer nerves results in the well-known experimental neurogenic hypertension. Despite their apparently important function in cardiovascular regulation, it is not clear what role they do play in the pathogenesis of hypertension. Since experimental neurogenic hypertension and human hypertension differ in several ways, any participation of the baroreceptors in the mechanism of either human or experimental non-neurogenic hypertension has been doubted by many investigators.

Muscular, respiratory and cardiovascular responses of quadriplegic persons to an F. E. S. bicycle ergometer conditioning program

Seven quadriplegic subjects participated in F. E. S. bicycle ergometry, three times per week, over an eight week period. Left thigh girth measured at 20 cm above the knee increased from 44.4 cm pre-training to 46.5 cm post-training (p less than 0.05), and right thigh girth increased from 44.3 cm to 46.2 cm (p less than 0.05). Forced vital capacity increased from 3.23 liters (pre-training) to 3.42 liters (post-training) and was significant at the p less than 0.05 level. Forced inspiratory capacity increased for 3.30 liters, pre-training, to 3.42 liters, post-training (p less than 0.05). FEV1 (liters) increased from 2.77, pre-training to 3.07 post-training (p less than 0.05). All three respiratory parameters were 55%-60% of that predicted for normals. Significant changes were also found in resting cardiovascular data. Mean resting heart rate, pre-training, was 51.4 beats per minute compared to 54.5 beats per minute, post-training, (p less than 0.05). Resting cardiac output, pre-training was 4.14 L/min. compared to 4.47 L/min., post-training (p less than 0.05). Further analysis of the cardiovascular data showed that the increased heart rate post-training was associated with a decrease in the P-R interval from 0.186 sec., pre-training to 0.170 sec., post-training (p less than 0.05). Also, the increase in cardiac output, post-training was matched by an increase in the cardiac index from 2.21 L/min./M, pre-training, to 2.36 L/min./M, post-training (p less than 0.05). A statistically significant difference in the heart rate response to the cold pressor test was demonstrated (p less than 0.05) and a similar difference in the amount of heart rate response was seen during the tilt table test (p = 0.05).

Baroceptor and Sympathetic Activity in Experimental Renal Hypertension in the Dog

Response to tetraethylammonium chloride was studied in normal and renal hypertensive dogs in which the carotid sinus was isolated and intrasinusal pressure was maintained by a pump. Normal, chronic, and acute renal hypertensive animals differed in their response at different intrasinusal pressure levels and indicated resetting of the baroceptors in the chronic hypertensive phase but not in the acute phase. This resetting may play a role in the maintenance of chronic renal hypertension.

Persistent Hypertension in the Dog Following Disruption of the Carotid Sinus Nerves and Subsequent Unilateral Renal Artery Constriction

Constriction of 1 renal artery in combination with disruption of the carotid sinus nerves resulted in moderate chronic hypertension in dogs. Hypertension persisted at the same level in some of the animals after removal of the kidney 1 year later, while in others blood pressure decreased somewhat though not to the prehypertensive control level. Narrowing of 1 renal artery without carotid nerve disruption did not lead to significant chronic hypertension. Disruption of the carotid sinus nerves alone, on the other hand, produced mild to moderate hypertension. Constriction of 1 renal artery, if performed several months after carotid nerve disruption, further increased the blood pressure in these animals. Tests of the carotid sinus nerves function by the occlusion reflex of the common carotids indicated a return of function several months after disruption in animals in which the carotid sinus nerves were only crushed. Hypertension persisted in these animals despite the return of the carotid sinus function. Tetraethylammonium choride given intravenously to combined carotid sinus-unilateral renal hypertensive dogs resulted in blood pressure decrease similar to that produced in normal animals. Glomerular filtration rate and renal plasma flow decreased, and filtration fraction increased in 3 dogs following production of the combined type of hypertension.