Measurement of cardiac output during exercise by the thermodilution and direct Fick techniques in patients with chronic congestive heart failure

Nine men with chronic stable congestive heart failure (New York Heart Association class II or III) were studied. Oxygen consumption was measured continuously and cardiac output (CO) determined by thermodilution and from the Fick equation at the end of each stage of treadmill exercise. CO measured by the 2 techniques was similar (r = 0.98) over the range of 2.5 to 13 liters/min (43 separate estimations). Tricuspid regurgitation developed in 2 patients during exercise, which resulted in unphysiologic estimates of CO (more than 30 liters/min) by thermodilution. In these circumstances estimation of CO by the direct Fick technique is superior. With this exception, CO measured by thermodilution was accurate even during exercise and provided results similar to those using the direct Fick technique.     

Calcium overload and mechanical function in posthypoxic myocardium: biphasic effect of pH during hypoxia.

Mechanical function and calcium accumulation in the myocardium during and after hypoxia were examined in the isolated but arterially perfused interventricular rabbit septum. The pH of the perfusate during hypoxia was varied from 7.4 to 6.6 by increase of the pCO2. All septa were reoxygenated for 30 min at pH 7.4. In the posthypoxic period the recovery of developed tension was greatest and the magnitude of contracture least in those septa perfused at pH 6.8 during hypoxia; calcium overload did not occur. By contrast, marked calcium overload (3.5 mumol/g wet wt) occurred in septa perfused at pH 7.4 during hypoxia. Reduction of pH to 6.6 during hypoxia did not result in a greater degree of recovery of developed tension or complete reversal of contracture in the posthypoxic period, and marked calcium overload was not prevented. These results indicate that: (1) partial recovery of mechanical function in the posthypoxic period can occur concurrent with a net gain of calcium; (2) the beneficial effects on recovery in the posthypoxic period in septa perfused at pH 6.8 during hypoxia may be in part released to prevention of calcium overload; (3) the beneficial effects of acidosis are lost when the perfusate pH is reduced to 6.6 during hypoxia.     

Effect of pH on ionic exchange and function in rat and rabbit myocardium.

The effects of pH variation on ionic exchange and mechanical function were studied in the arterially perfused rat and rabbit septa. The pH and PCO2 of the control perfusate were 7.40 and 39 mmHg, respectively. In the rabbit septum a metabolic acidosis (pH equals 6.82, PCO2 equals 39 mmHg) caused a loss of 16% of control tension in 12 min. Na+ and K+ exchange were unaltered. A comparable respiratory acidosis (pH equals 6.81, PCO2 equals 159 mmHg) caused a 51% loss of tension in 2 min. Na+ exchange was unaltered but K+ efflux fell from 8.9 +/- 0.6 (mean +/- SE) to 4.9 +/- 0.3 mmol/kg dry wt per min (P less than 0.001, n equals 10). A net gain of K+ of 16.9 +/- 1.7 (n equals 14) mmol/kg dry wt occurred and was attributable to a delayed fall in K+ influx relative to efflux over 15 min. The net gain could not be mimicked by epinephrine administration or blocked by propranolol and was absent in the beating rat septum and the quiescent rabbit septum. These results suggest that the net uptake of K+, which appears to be dependent on a period of depolarization, and the changes of contractility are controlled by the H+ ion concentration at a cellular site whose exchange with the extracellular space is characterized by a considerable restriction of diffusion. Changes of contractility are not related to the net uptake of K+.     

Calcium antagonists: definition and mode of action

Summary The term calcium antagonist has been used for more than a decade to describe a group of drugs whose negative inotropism is overcome by calcium. Because this term lacks specificity with respect to a precise mode of action, and implies a classical receptor-agonist-antagonist relationship, its continued use should be questioned. Drugs belonging to this group are verapamil, D600, nifedipine and diltiazem. They inhibit the slow inward current of the action potential and would more appropriately be called slow channel inhibitors. The group is heterogenous and may have to be subclassified.The negative inotropism of these drugs can be attributed to a reduction of the slow calcium current. The function of most intracellular organelles is unaffected. Studies with radioactively labelled verapamil show tight binding to glycolipids or glycoproteins in the sarcolemma. Consequent change in the conformational state of the cell membrane could inhibit the slow calcium current.The ability of these drugs to protect heart muscle against the deleterious effects of ischaemia and reperfusion may reflect their negative inotropism, with consequent maintenance of tissue ATP above the levels needed to maintain intracellular Ca²⁺ homeostasis, rather than a direct inhibitory effect on calcium influx during ischaemia or on reperfusion.With 6 figures and 1 tableThe investigations were carried out during the tenure of a grant from the Medical Research Council of Great Britain and the NH and MRC of Australia.     

Comparison of ventricular long-axis function in patients with cardiac amyloidosis versus idiopathic restrictive cardiomyopathy

To investigate ventricular long-axis function in cardiac amyloidosis (CA) and idiopathic restrictive cardiomyopathy (IRC), 16 patients with CA and 14 with IRC were studied. Left ventricular (LV) long-axis function was depressed in all patients with CA compared with only 36% of patients with IRC. Impairment in longitudinal function was clearly evident, even if fractional shortening and LV filling were normal. Ventricular long-axis function may be used as a sensitive marker of early systolic dysfunction. CA and IRC have quite distinct pathophysiologic profiles, raising some concerns about the appropriateness of considering them as 2 subtypes of a single nosographic entity.     

Heart rate response during exercise predicts survival in adults with congenital heart disease.

OBJECTIVES: To assess the prognostic value of heart rate response to exercise in adult congenital heart disease (ACHD) patients. BACKGROUND: An abnormal heart rate response to exercise is related to autonomic dysfunction and may have prognostic implications in ACHD. METHODS: We identified 727 consecutive ACHD patients (mean age [+/- SD] 33 +/- 13 years) with varying diagnoses and without pacemakers. Peak oxygen consumption (peak VO2), resting heart rate, and the increase in heart rate from resting level to peak exercise ("heart rate reserve") were measured. We also quantified the decrease in heart rate ("heart rate recovery") after cessation of exercise. RESULTS: During a median follow-up of 28 months, 38 patients died. Lower values of heart rate reserve, peak heart rate, heart rate recovery, and peak VO2 (p < 0.01 for each) were associated with increased mortality in univariate analysis. Furthermore, heart rate reserve predicted mortality independently of antiarrhythmic therapy, functional class, and peak VO2. Stratifying patients by diagnostic groups revealed that a lower heart rate reserve was also associated with a greater risk of death in patients with complex anatomy, Fontan circulation, and tetralogy of Fallot (p < 0.05 for each). CONCLUSIONS: An abnormal heart rate response to exercise identifies ACHD patients with a higher risk of mortality in the midterm, even after accounting for antiarrhythmic medication and exercise capacity. Heart rate reserve is a simple and inexpensive way to identify ACHD patients at higher mortality risk.