Central and regional hemodynamic effects and neurohumoral consequences of minoxidil in severe congestive heart failure and comparison to hydralazine and nitroprusside

Minoxidil is a potent oral vasodilator of potential value in patients with congestive heart failure (CHF), although preliminary studies show that it causes fluid retention. To test whether minoxidil acts primarily as an arterial vasodilator in CHF, it was compared with hydralazine and nitroprusside. To evaluate its chronic efficacy and mechanism of fluid retention, the effects of minoxidil (7 patients) were compared, in a double-blind manner, with those of hydralazine (8 patients) on central and regional hemodynamics and the renin-angiotensin-aldosterone and sympathetic nervous systems. There was no demonstrable difference in the central hemodynamic effects of minoxidil and hydralazine in the dosages used. After 6 hours both drugs increased cardiac index (minoxidil group, from 1.65 ± 0.29 to 2.26 ± 0.40 liters /min/m², p < 0.0001; hydralazine group, from 1.88 ± 0.61 to 2.34 ± 0.90 liters/min/m², p < 0.0001), decreased systemic vascular resistance and increased heart rate without change in pulmonary arterial, pulmonary capillary wedge or right atrial pressures. Nitroprusside effects differed from those of minoxidil and hydralazine with respect to heart rate (p < 0.005) and mean pulmonary arterial (p < 0.007) and right atrial (p < 0.009) pressures. Nitroprusside also decreased relative hepatomesenteric flow compared with the other 2 agents (p < 0.005). Neither renal blood flow, glomerular filtration rate, filtration fraction, nor urinary sodium excretion were significantly altered acutely by any of the 3 drugs. Minoxidil and hydralazine did not differ in their neurohumoral effects: Both agents produced an increase in plasma norepinephrine concentration (p < 0.003) and plasma renin activity (p < 0.04), but no change in plasma epinephrine or aldosterone concentrations. After 1 week of double-blind therapy, fluid retention was a greater problem with minoxidil than with hydralazine. Thus, minoxidil behaves primarily as an arterial vasodilator in CHF, fluid retention is a severe adverse effect, and the greater degree of fluid retention with minoxidil than hydralazine is not attributable to differing acute effects on total renal blood flow or function, or differing effects on the renin-angiotensin-aldosterone or sympathetic nervous systems.     

High sodium-low potassium environment and hypertension

The high sodium-low potassium environment of civilized people, operating on a genetic substrate of susceptibility, is the cardinal factor in the genesis and perpetuation of “essential” hypertension. The noxious effects begin in childhood, when habits of excess salt consumption are acquired at the family table, and are perpetuated by continuing habit and by increasing use of convenience and snack foods with artificially high concentrations of sodium and low levels of potassium. Present methods of food preparation leach out the protective potassium. Extradietary sodium chloride is a condiment, not a requirement. Some primitive populations clearly preferred potassium chloride to sodium chloride.Chronic expansion of extracellular fluid volume induced by excess salt consumption causes the central and peripheral circulatory regulatory mechanisms to work at cross purposes, resulting in increased arterial pressure. The protective effect of potassium is dramatic and easily demonstrable in animals and man but its mechanism is not known. It cannot be entirely a direct effect on blood pressure because rats protected with extra potassium against a moderately high salt intake live much longer than control rats but have the same elevated blood pressures. In hypertension with a demonstrable “cause,” the high sodium-low potassium environment makes a bad matter worse.In nature, feral man and his forebears were not confronted with excessive sodium and deficient potassium; indeed, the reverse was the case. Evolution has provided powerful mechanisms for conserving sodium and eliminating potassium, but no efficient physiologic mechanisms for conserving potassium and eliminating excess sodium. Most laboratory animal “control” diets contain an amount of sodium that fully suppresses aldosterone secretion, and the same is true of the “average” diet of the American people. Inadequate attention to dietary sodium and potassium makes many studies in both animals and man of uncertain validity.Internally, essential hypertension is an exceedingly complex mosaic of physiologic interactions. Viewed from outside, it is a disorder for which genetic material sets the stage; excessive sodium precipitates it and perpetuates it. Extra salt makes all forms more rapidly progressive and accelerates the onset of terminal events; extra potassium is everywhere protective. When an entire population eats excessively of salt, hypertension will develop among those genetically susceptible, but epidemiologic studies of salt versus blood pressure will not show a relation of salt to hypertension. This is the saturation effect.Low sodium diets are therapeutically effective but generally regarded as an impossible or an unnecessary nuisance. Effective prevention programs must be instituted at as early an age as possible. The efficacy of a prophylactic/therapeutic low sodium-high potassium diet should be weighed against the uncertain hazards of a lifetime of pill taking.     

Effect of verapamil on retrograde conduction in atrioventricular nodal reentrant tachycardia

Using His bundle electrograms, incremental ventricular pacing and the ventricular extrastimulus (V2) technique, the effects of intravenous verapamil, 0.2 mg/kg, on retrograde atrioventricular (AV) nodal conduction during ventricular pacing, premature ventricular stimulation (H2A2 interval) and paroxysmal supraventricular tachycardia (SVT) (H-Ae interval) were evaluated in 11 patients with AV nodal reentrant tachycardia. During the control study, SVT could be induced in all 11 patients. After verapamil administration, SVT or atrial echo beats could be induced in 5 patients. Verapamil produced ventriculoatrial (VA) block at a longer cycle length than that during the control study in 10 of 11 patients (295 +/- 27 vs 352 +/- 40 ms, p less than 0.01), but prolonged H2A2 interval in only 5 of 11 patients (37 +/- 6 vs 60 +/- 31 ms, p less than 0.05). In all 5 patients with persistence of inducible SVT or atrial echo beats after verapamil treatment, the H-Ae interval remained unchanged even though in 4 of these 5 patients VA conduction time or H2A2 interval was prolonged. Correlation between the paced cycle length which induced VA block, the shortest V1H2 interval achieved during premature ventricular stimulation and the cycle length of SVT revealed that in all instances in which verapamil induced VA block at a longer cycle length than in controls but did not prolong H2A2 or H-Ae interval, the shortest V1H2 interval and the cycle length of SVT (H-H interval) were significantly longer than the ventricular paced cycle length which produced VA block.(ABSTRACT TRUNCATED AT 250 WORDS)     

The capillary factor in myocardial infarction

The deleterious effect of lack of blood supply or of oxygen on capillaries in general is well known. In the studies reviewed in this paper, the results of the earlier work of others on the effect of temporary myocardial ischemia are confirmed and extended. The vulnerability of the myocardial capillaries to ischemic, asphyxic and anoxic insult is demonstrated. Evidence is cited to suggest that this vulnerability occurs because the heart is a continuously working muscle, highly sensitive to ischemia, asphyxia and anoxia.     

Tissue valve replacement of prosthetic heart valves for thromboembolism

Twenty-five patients who had repeated thromboemboli from a prosthetic mitral valve were treated with reoperation using a tissue valve prosthesis. Reoperation was performed an average of 4.0 years after the original valve replacement in 14 men and 11 women, with an average age of 50 (range 35 to 65) years. A stented allograft was used in the first 7 patients and a porcine xenograft in the last 18 patients. There were one hospital death and two late deaths. With the first prosthetic valve there were 66 documented embolic episodes in 101.5 patient years (0.65 embolus/year). Only four embolic episodes in 67.4 patient years (0.059 embolus/year) occurred after tissue valve replacement (P < 0.001). These results indicate that in patients with recurrent or severe embolization after prosthetic heart valve replacement, rereplacement with a tissue prosthesis can be safely performed and significantly reduces the likelihood that additional embolic episodes will occur.     

Sounds of the heart in diastole

Cardiac diastole usually is acoustically silent even though several hemodynamic events take place in this phase of the cardiac cycle. In some healthy subjects and in many patients with cardiovascular alterations one or more “extra” heart sounds may be heard in diastole, and in them the distinction between normal and abnormal heart sounds must be established. In general, diastolic sounds may be spontaneous in nature or iatrogenic, that is, a consequence of replacement of the atrioventricular (A-V) valve with a caged-poppet prosthesis or a result of pervenous pacemaker implantation. The majority of the sounds emanate from the chambers of the heart. This presentation discusses normal and abnormal ventricular filling sounds, opening snap, “tumor plop,” pericardial knock, prosthetic A-V valve click and pacemaker-induced sound.     

Mechanism of caffeine-induced arrhythmias in canine cardiac purkinje fibers

The effects of caffeine were studied in canine cardiac Purkinje fibers perfused in vitro. The study revealed that (1) caffeine induces an oscillatory potential (V_os) superimposed on early diastolic depolarization in driven fibers; (2) V_os magnitude increases (within limits) with the concentration of caffeine (0.5 to 3 mM) and as a function of time of exposure; (3) if the drive is interrupted, V_os may attain the threshold and initiate spontaneous repetitive activity; (4) caffeine increases the rate of discharge in spontaneously active fibers, also through a V_os; (5) V_os shows the same characteristics as under other conditions of calcium overload; that is, it disappears after a long pause, increases after a shorter pause, can be suppressed by overdrive and can initiate spontaneous discharge at normal or depolarized levels; (7) V_os is dependent on cellular calcium as it appears at lower caffeine concentrations in fibers that are loaded with calcium by increasing extracellular calcium concentration [Ca]_o, by decreasing extracellular sodium concentration [Na]_o or by administering strophanthidin; (8) caffeine-induced V_os is made to peak sooner and to initiate fast spontaneous rhythms by norepinephrine; (9) V_os is reduced by low [Ca]_o but not by propranolol. It is concluded that caffeine causes an oscillatory potential that is modulated by cellular calcium, and this V_os can induce arrhythmias.     

Diagnosis and management of complications of prosthetic heart valves

Complications after heart valve replacement remain a substantial source of morbidity and mortality despite continuing advances in surgical care and prosthetic design. Infectious endocarditis occurs in about 4 percent of patients and may appear early (within 60 days) or late after operation. Endocarditis of early onset is commonly due to staphylococcal, fungal or gram-negative organisms and is fatal in 70 percent or more of cases. Infection of late onset is more often of streptococcal origin and the mortality rate is lower, about 35 percent. With either type, prompt recognition, vigorous and appropriate antimicrobial therapy and early consideration of surgical intervention are crucial.

The postperfusion and postpericardiotomy syndromes are relatively common and relatively benign syndromes associated with postoperative fever. Their recognition is important to prevent confusion with endocarditis or sepsis and thus to reassure the patient and physician. Treatment is primarily symptomatic. Intravascular hemolysis occurs with most prosthetic heart valves but is more common with certain prostheses and with paraprosthetic valve regurgitation, with significant hemolytic anemia in 5 to 15 percent. Oral iron replacement therapy is effective in the majority of patients, but occasionally blood transfusion or reoperation for leak around the prosthesis is necessary. Prosthesis dysfunction due to thrombus may be recognized clinically by recurrence of heart failure, syncope, cardiomegaly and altered prosthetic valve sounds or new murmurs. Hemodynamic studies verify the diagnosis, and prompt reoperation is indicated for this potentially lethal problem. Systemic embolization has decreased markedly with the introduction of cloth-covered prostheses and is frequently related to erratic or ineffective anticoagulant therapy. We continue to recommend anticoagulant therapy for all patients with prosthetic heart valves unless there is a major contraindication.     

Elevated catecholamines during cardiac surgery: consequences of reperfusion of the postarrested heart

This study determines whether reperfusion of the heart with elevated blood levels of epinephrine (E) and norepinephrine (NE) during cardiac surgery produces deleterious effects. The study was conducted in 60 patients undergoing coronary artery bypass surgery. Arterial catecholamine values increased significantly (p less than 0.05), from prebypass control levels of 152 +/- 29 and 327 +/- 30 pg/ml of E and NE, respectively, to 415 +/- 78 and 554 +/- 49 pg/ml, at initiation of perfusion of the heart after the aortic cross-clamp was removed. Serial measurement of arterial (A) and coronary sinus (CS) E, NE, potassium, lactate, PO2 and CK-MB revealed that during 10 minutes of reperfusion the heart extracted E (positive A-CS difference, p less than 0.05), but that the NE A-CS difference was 0. The CS effluent contained significantly (p less than 0.05) higher concentrations of potassium, lactate and CK-MB during reperfusion than before aortic occlusion. There was no significant correlation of arterial E and NE, CS E and NE or A-CS differences in E and NE with myocardial release of lactate, potassium or CK-MB. There was a weak association (r = 0.4, p less than 0.01) between coronary sinus CK-MB and aortic occlusion time. Maximal arterial E and NE values did not correlate with 10-hour postoperative (maximal) CK-MB values. These results indicate that reperfusion of the postarrested ischemic heart with high levels of endogenously released catecholamines does not worsen ischemia or contribute significantly to myocardial damage.     

Calcification of aortic versus mitral porcine bioprosthetic heart valves: a radiographic study comparing amounts of calcific deposits in valves explanted from the same patient

Calcium detected by radiography was compared in 10 pairs of aortic and mitral glutaraldehyde-treated porcine bioprosthetic heart valves explanted from 10 patients (7 men and 3 women), aged 19 to 68 years (mean 43). Both valves of 6 pairs of valves had undergone primary tissue failure (revealed by cardiac catheterization and angiography) and 1 valve of the other 4 pairs of valves had undergone primary tissue failure. These porcine valves had been implanted from 2 1/4 to 9 years (mean 5 3/4). All 20 explanted valves contained calcium. The grade of calcium was the same in 4 pairs of valves (grade 2+ or 3+), and 1 grade different in 4 pairs of valves (grade 1+ to 4+), with the greater calcium evenly divided between the 2 valve positions. There was more than 1 grade greater mitral valve calcium in 2 pairs of valves (grade 3+ and 4+ mitral vs 1+ and 2+ aortic, respectively). Thus, calcium is usually present in both aortic and mitral valve positions when bioprosthetic valves of this type in either valve position fail as a result of primary tissue failure, and radiographic calcium in porcine bioprosthetic valves is usually similar in grade in both the aortic and mitral valve positions.     

Platelet survival in patients with prosthetic heart valves

Chromium-51 platelet survival studies were carried out in 20 patients with a prosthetic heart valve. Only 1 of 10 patients with a prosthetic mitral valve had a significantly shortened platelet survival time, and the mean value of 8.3 ± 0.96 (±1 standard deviation) days was not significantly different from that of normal control subjects (8.9 ± 0.75 days). Four of 10 patients with an aortic prosthesis had a shortened platelet survival time, and the mean value of 7.8 ± 0.10 days in this group differed significantly from the normal control value (P < 0.05). Treatment with aspirin did not appear to alter platelet survival but, when combined with Coumadin therapy, resulted in marked prolongation of bleeding time. Our results do not support the concept that thrombus formation on the prosthesis is the cause of the shortened platelet survival time since thrombus formation is more likely to occur in mitral than aortic prostheses. Reduced platelet survival time secondary to damage by the prosthesis, similar to the problem of hemolysis in red blood cells, is a more likely explanation.     

Effect of catheter position on the initiation of atrial echoes with atrial pacing and premature stimulation in patients with accessory pathways

Eleven patients with an accessory pathway and reciprocating tachycardia were studied using both fixed rate atrial pacing and the atrial extrastimulus technique. Six of the patients had an accessory pathway that conducted in both the anterograde and retrograde direction; but the effective refractory period of their accessory pathway in the anterograde direction was relatively long and was greater than the longest coupling intervals that initiated atrial echoes. Five patients had an accessory pathway that conducted only in the retrograde direction.The extrastimulus technique could be used with stimulation sites near to and remote from the accessory pathway in 10 of the 11 patients. Atrial echoes were initiated by a single atrial extrastimulus at both sites in 7 of the 10 patients, and in each patient the upper limit of the echo zone was longer with stimulation at the site near the accessory pathway. In the other three patients atrial echoes were initiated only during stimulation at the site near the acessory pathway because either atrial refractoriness or atrioventricular nodal refractoriness was encountered before the echo zone was entered during stimulation at the site remote from the accessory pathway.Differences in the longest cycle length that initiated an atrial echo during fixed rate atrial pacing were similarly demonstrated in three patients. In these three patients, pacing at the site near the accessory pathway initiated echoes at a longer cycle length than pacing at the site remote from the accessory pathway. In three other patients the electrophysiologic characteristics of atrioventricular conduction prevented a demonstration of these differences. Catheter position is an important variable in the initiation of atrial echoes in patients with accessory pathways.     

Salmonella bacteremia in patients with prosthetic heart valves

During 1982 and 1983, five patients with prosthetic heart valves and documented Salmonella bacteremia were admitted to the Instituto Nacional de Cardiologia in Mexico City. The clinical and microbiologic features in this group of patients are described, as well as the therapeutic implications when Salmonella bacteremia is present in patients with heart prostheses. None of the patients had evidence of infectious endocarditis; however, all received prolonged parenteral antimicrobial therapy for at least four weeks with ampicillin or chloramphenicol, with excellent clinical response.     

Determinants of reperfusion cardiac electrical activity after cold cardioplegic arrest during coronary bypass surgery

In a prospective study of 99 patients with coronary artery disease, reperfusion of the heart after a period of ischemia (protected by contemporary techniques of myocardial preservation) resulted in spontaneous resumption of cardiac electrical activity in 53%, spontaneous defibrillation in 10%, reperfusion ventricular fibrillation (VF) in 32% and indeterminate rhythm in 5%. In hearts spontaneously developing rhythms excluding VF (as opposed to hearts requiring direct-current shock), factors significantly associated were a higher plasma potassium concentration (5.2 vs 4.8 mEq/liter), shorter reperfusion time (1 vs 4 minutes), higher plasma magnesium concentration (1.36 vs 1.25 mg/dl) and a lower myocardial temperature (27 vs 32 degrees C). The duration of ischemia, arterial blood gas levels, plasma catecholamine levels, plasma ionized calcium levels, volume of cardioplegia and mean arterial pressure did not relate to occurrence of spontaneous episodes. However, VF developed in 39 of 52 patients (75%) with spontaneous resumption of electrical activity. This event was associated with lower myocardial temperature. Thus, direct-current shocks were ultimately required in 77 of the 99 patients (78%). Although certain thermal, biochemical and hemodynamic variables facilitate spontaneous resumption of cardiac rhythm, the development of VF may negate the potential benefit of this event in the prevention of myocardial damage from direct-current defibrillation.     

Reflex heart block: Baroreflex, chemoreflex and bronchopulmonary reflex causes

Reflex heart block was studied in 20 dogs anesthetized with sodium pentobarbital and in 5 trained unanesthetized dogs. Three different vagal reflexes were produced: the Marey response during hypertension caused by administering methoxamine, a cardiogenic hypertensive chemoreflex activated by injection of serotonin into the left atrium and the Hering-Breuer reflex observed during normal respiration of unanesthetized dogs. In every dog during any of the three reflexes heart block was consistently observed after the normal slowing response of the sinus node had been selectively eliminated by the direct perfusion of 10 μg of atropine into the sinus node artery. This was a uniform response despite its being variously produced by a pressor reflex, a chemoreflex or an extracardiac bron-chopulmonary reflex. Transient heart block is therefore to be anticipated during reflexes with vagal efferent components if for any reason the sinus node is incapable of slowing suitably. The possible clinical relevance of these experimental observations is discussed.