Effects of Chronic Hypoxia during Maturation on the Negative Chronotropic Effect of [H⁺] on the Rabbit Sino-Atrial Node

Abstract

Previous studies in our laboratory have shown an effect of 12 weeks of hypoxia on the electrophysiology of the heart. This study was designed to determine the effects of hypoxia for shorter periods (1,2,3 and 6 weeks) on the neonatal heart as well as the chronotropic effects of [H⁺] on sino-atrial automaticity. Rabbits (2 days of age) were raised for 1, 2, 3 or 6 weeks in either a normal or hypoxic environment. At the end of 1, 2, 3 or 6 weeks, they were killed and studied using an isolated sino-atrial tissue preparation and standard microelectrode techniques. Measurements of hematocrit, ventricular weight and ventricular total protein were made. Right ventricular hypertrophy appeared at 2 and 3 weeks in the hypoxic hearts. There was no difference in left ventricular weight or total protein between normal and hypoxic groups over the time studied. Both the basal and maximal (isoproterenol stimulated) spontaneous rates decreased with age. The baseline and maximal rates from hypoxic rabbits were significantly less than those from normal rabbits at 3 and 6 weeks (p < 0.05). The net negative chronotropic effect of elevated [H⁺] was more pronounced in the hypoxic than the normal preparations at 3 and 6 weeks. In summary, neonates raised in hypoxia for as short a period as 3 weeks show right ventricular hypertrophy and a decrease in sino-atrial automaticity. The net negative chronotropic effect of [H⁺] is enhanced with development and chronic hypoxia.

Effect of Growth and Maturation in a Hypoxic Environment on Maximum Coronary Flow Rates of Isolated Rabbit Hearts

“…Peak reactive hyperemic flow rates were 25% higher at age 5 wk and 34% higher at age 12 wk in hearts of hypoxically raised compared with normoxically raised rabbits. DISCUSSION Previous studies in which the present experimental method for raising rabbits in environmental hypoxia was used have demonstrated increased right but not left ventricular weight and protein content by age 3 wk (9,10). Consistent with these findings, the present results show increased right ventricular segment weight but unchanged left ventricular segment weight in hypoxically raised rabbits at age 5 wk.…”

“…A method for raising rabbits in a hypoxic environment, beginning in the neonatal period, has been established at the University of Florida and used in our laboratory as an experimental model for studying the effects of hypoxemia on the maturing cardiovascular system (9,10). The purpose of this study was to determine the effects of growth and maturation of rabbits in this hypoxic environment on the ability to perfuse myocardium.…”

Ischemia alters the electrical activity of pacemaker cells isolated from the rabbit sinoatrial node

“…Another difference between our study and previous ones is that pH 6.6 ischemic Tyrode solution did not slow pacemaker activity, possibly because this treatment was too brief to activate I K(ATP) . In comparison, Posner and co-workers (33) found that the mean BR of isolated right atria was slowed significantly from 173 to 129 beats/min when rabbits were raised in a hypoxic environment (PO 2 ϭ 65 mmHg) for 3 wk. They also showed that acidosis alone could slow BR dramatically (on average, from 173 to 18 beats/ min).…”

Genesis and Regulation of the Heart Automaticity

“…6). Acidosis of the extracellular environment induces negative chronotropism (399,469). This mechanism can be responsible for bradycardia during parturition (469) or under ischemic conditions (164).…”