Effect Of Cardiac Denervation Research Articles

Physiology and Redundancy

This year's Walter B. Cannon lecture is titled “Is Physiology Redundant?” I chose this title to reflect two divergent definitions of the word redundant. In the first definition, redundant can mean extra, nonessential, or no longer needed. In the 1980s and 1990s, the view that physiology as a

Effects of cardiac denervation on β-adrenergic receptor subsensitivity phenomenon in myocardium

Effects of cardiac denervation on β-adrenergic receptor subsensitivity phenomenon in myocardium

Effects of cardiac denervation on development of heart failure and catecholamine desensitization.

Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depletion of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592+/-79 pg/mL) compared with intact dogs (576+/-81 pg/mL) in heart failure. Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.

Effects of cardiac denervation on coronary and systemic circulation

The effects of cardiac denervation on coronary circulation and systemic hemodynamics were examined in patients who underwent coronary artery bypass grafting for a totally occluded left anterior descending coronary artery. The results in 14 patients who had undergone a combination of bypass grafting and intrapericardial denervation (group I) were compared with those in 19 patients who had undergone only bypass grafting (group II). The heart rate was 110 ± 4.9 beats/min in group I and 104 ± 3.7 beats/min in group II after denervation. Although the cardiac index was not significantly different between the two groups, the calculated systemic vascular resistance index of group I (1,35B ± 111 dynes · s · cm −5 · m 2) was significantly lower ( p < 0.02) than that in group II (1,713 ± 75 dynes · s · cm −5 · m 2). The end-diastolic coronary resistance was significantly lower ( p < 0.05) in group I (0.59 ± 0.05 mm Hg · mL −1 · min −1) than that in group II (1.04 ± 0.14 mm Hg · mL −1 · min −1), and the enddiastolic graft flow/mean graft flow ratio was 1.56 ± 0.05 in group I and 1.28 ± 0.04 in group II ( p < 0.01). The plasma norepinephrine concentration in group I (223 ± 52 pg/mL) was significantly low ( p < 0.05) compared with that in group II (328 ± 39 pg/mL) after denervation. Thus, cardiac denervation may have a beneficial effect on systemic hemodynamics and coronary circulation.

Effect of cardiac denervation on cardiorespiratory responses to exercise in goats

The purpose of this study was to determine whether intact cardiac innervation and a normal cardiovascular (CV) response are required for a normal ventilatory (VE) response to mild and moderate treadmill exercise in awake goats. Accordingly, we measured CV and respiratory responses to two levels of exercise in seven normal (N) and six cardiac-denervated (CD) goats. Evidence of surgical CD included 1) absence of a cardiac response during surgery when the left thoracic cardiac nerves, thoracic vagi, and right and left stellate ganglia were electrically stimulated, 2) total and 80% attenuation of baroreflex changes in heart rate (HR) when arterial blood pressure was raised or lowered, respectively, by infusion of vasoactive agents in awake goats, and 3) attenuation of the CV responses to exercise. At each level of exercise in the CD goats, the HR response was significantly reduced relative to the response observed before CD (P less than 0.05) and the recovery HR response was delayed. Cardiac index increased in a work rate-dependent manner in N and CD goats but was significantly lower in the CD animals (P less than 0.05). Hypotension was consistently observed during exercise following CD. There was no effect of CD on steady-state VE at any metabolic rate or on the VE-O2 uptake relationship (P greater than 0.05). The rest-to-work and work-to-work transition responses of arterial PCO2 were similar between N and CD goats, but there was a tendency toward greater hypocapnia at the exercise onset in CD goats at the highest work rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cardiac denervation on levels of neuronal survival factors for cultured autonomic neurones

The content of survival factors for sympathetic, sensory and parasympathetic neurones in the heart was examined after denervation with either 6-hydroxydopamine or vagal transection. There was a correlation between the type of nerve sectioned in vivo and the type of neurone whose survival in vitro was enhanced by the presence of denervated target tissue.

Effect of cardiac denervation on myocardial oxygen consumption in vitro: R. B. Wanless, Angela J. Drake-Holland, M. I. M. Noble. The Midhurst Medical Research Institute, West Sussex. GU29 OBL. England

Effect of cardiac denervation on myocardial oxygen consumption in vitro: R. B. Wanless, Angela J. Drake-Holland, M. I. M. Noble. The Midhurst Medical Research Institute, West Sussex. GU29 OBL. England

The effects of cardiac denervation on renal function.

Assessment of certain parameters of renal function were carried out before and 1 wk after total denervation of the heart by a method which leaves nerves to other organs intact. No changes in mean blood pressure, central venous pressure, cardiac output, GFR, or RPF were noted after cardiac denervation. UNaV after a low sodium diet was similar during a control period before and after denervation, but in response to expansion of the plasma volume a 3-fold greater natriuresis was seen in the denervated group. Alterations in the filtered load of sodium, the secretion of aldosterone, or most of the recently described physical and compositional factors known to influence sodium excretion cannot adequately explain this natriuresis. Expansion of an already augmented plasma volume after denervation or the possibility of a natriuretic or antinatriuretic factor with afferents interrupted in the process of cardiac denervation must be considered as etiologic factors.

Absence of effect of cardiac denervation and induced right ventricular failure on canine myocardial norepinephrine binding sites.

Myocardial sensitivity to catecholamines appears to be altered in chronic cardiac denervation and failure. We have studied in vitro the binding of tritiated norepinephrine (3H-NE) to binding sites in myocardial membrane fractions prepared from canine right and left ventricles. Twenty-six dogs were studied; eight were normal controls, two had sham operations, eight had cardiac denervation, and eight had cardiac failure. Myocardial membranes were incubated with 5 × 10-9 mol/1 3H-NE in vitro and displacement studies with unlabelled norepinephrine performed. Computer-generated Scatchard plots indicated K (affinity constant of binding in 1/mol x 106) and q (number of binding sites in mol/mg of protein x 10-10). No group differed significantly from normal and sham controls. These results suggested that altered myocardial sensitivity to catecholamines in cardiac denervation and failure is not due to altered affinity or concentration of norepinephrine binding sites.

The effects of cardiac denervation on body fluids.

SummaryEvaluation of certain parameters of body fluids was carried out before and 1 wk following total denervation of the heart by a method which leaves nerves to other organs intact. In comparison with the normal state, dogs with denervated hearts showed an elevation of blood volume due almost entirely to an increase in the plasma component, little change in the volume of the interstitial space, and a large deficit of intracellular water. A loss of solute and water in the urine with solute leaving the cells to replace urinary losses could account for the decrease in the volume of the intracellular compartment. In the face of an elevated blood volume the concentration of ADH in plasma was diminished which was associated with a decreased urinary osmolality and increased urine volume following surgery.

Effects of cardiac denervation on blood pressure and heart rate during natural sleep in the cat.

Comparison of blood pressure and heart rate changes in synchronized and desynchronized sleep before and after various kinds of heart denervations has shown that the blood pressure fall occurring in sleep is independent of any nervous influence exerted on the heart. Bradycardia is mostly due to increased vagal activity.

EFFECT OF CARDIAC DENERVATION ON THE MAXIMAL CAPACITY FOR EXERCISE IN THE RACING GREYHOUND.

Ten consecutive time trials were run at 2-day intervals by six racing greyhounds over a 5/16-mile track. Cardiac denervation was then performed on four dogs, and a sham operation that included removal of the pericardium was performed on two dogs. After cardiac denervation, one dog died and another was rejected from the study because of a massive intrathoracic hemorrhage. The time trials were repeated with the addition of telemetry of the heart rate in the four survivors. There was no significant difference between mean preoperative and postoperative race times in the control group. The mean postoperative running speeds of 33.6 and 33.3 mph in the denervated group, although representing a significant slowing of 1.1 and of 2.1 mph, respectively, from preoperative values, indicate the adequate manner in which the denervated heart meets the circulatory demands of maximal running effort. cardiac output; heart rate and exercise Submitted on March 11, 1964