Mark D Parrish

Global myocardial ischemia in the newborn, juvenile, and adult isolated isovolumic rabbit heart. Age-related differences in systolic function, diastolic stiffness, coronary resistance, myocardial oxygen consumption, and extracellular pH.

Controversy persists over the relative tolerance of the immature myocardium to global ischemia. Thus, we evaluated the physiologic effects of 30, 60, and 180 minutes of global ischemia in an isolated, isovolumic rabbit heart model, at 3 different ages: newborns (less than 1 week of age) (n = 36), juveniles (4 to 6 weeks old) (n = 36), and adults (5 to 7 months old) (n = 36). Following 30 and 60 minutes of ischemia, respectively, adults recovered 87 ± 4% (mean ± SEM) and 90 ± 7% of baseline systolic function, and juveniles recovered 91 ± 10% and 85 ± 8%. In contrast, newborns recovered only 27 ± 6% and 28 ± 4% of baseline systolic function (p<0.05 compared to adults and juveniles). During ischemia, newborn hearts became stiff more rapidly, reaching 361 ± 46% of baseline stiffness by 60 minutes, whereas adults and juveniles were at 122 ± 33% and 92 ± 18% of baseline stiffness (p<0.05 newborns compared to adults and juveniles). With reperfusion after 60 minutes of ischemia, the work efficiency of the newborn heart deteriorated to 39 ± 7% of baseline, compared with 95 ± 7% and 91 ± 7% of baseline efficiency in the adult and juvenile hearts (p<0.05, newborns compared to adults and juveniles). The ratio of tissue wet-to-dry weights were similar in all age groups after ischemia. However, tissue pH was significantly higher in newborns during ischemia (6.54 ± 0.06, 6.69 ± 0.07, and 6.85 ± 0.09 in adults, juveniles, and newborns, after 60 minutes of ischemia) (p<0.05 newborns versus adults). We conclude that the newborn rabbit hearts are more susceptible to ischemic injury than the juvenile and adult hearts. (Circulation Research 1987;61:609-615)

Exercise radionuclide ventriculography in children: normal values for exercise variables and right and left ventricular function.

Thirty two children (aged 5-19 years) with no clinical evidence of significant cardiovascular disease undertook continuous staged supine exercise on a bicycle ergometer. Multigated radionuclide ventriculography was performed at rest and during each exercise stage. Exercise duration and total workload both increased with age. Aerobic work correlated better with age than did total work. In most children the ejection fraction for both ventricles increased by at least 5% with exercise. Right ventricular ejection fraction did not decrease with exercise in any subject but left ventricular ejection fraction decreased by 2% and 9% in two. The response of end diastolic volume to exercise was variable, but there was a consistent decrease in mean (SD) end systolic volume of the left (29(22)%) and right (30(19)%) ventricles. Cardiac index (mean (SD)) increased by 234(65)% with exercise. The left ventricular:right ventricular end diastolic volume ratio (mean (SD)) at rest was 1.26(0.26). It is concluded that exercise radionuclide ventriculography is an excellent technique for a combined assessment of exercise capacity and an evaluation of ventricular size and performance in children. These values for supine bicycle exercise in children without significant cardiovascular disease will be useful for future comparisons with other groups.

Beneficial effects of perfluorochemical artificial blood on cardiac function following coronary occlusion

This study compares the effects of perfluorochemical artificial blood versus whole blood on the systolic and diastolic function of regionally ischemic myocardial preparations. Regional ischemia was produced by ligation of the circumflex coronary artery in isolated, blood-perfused rabbit hearts. Three minutes after occlusion, half the hearts were switched from the blood perfusate to perfluorochemical artificial blood; the other half continued to be perfused with blood. Isovolumic left ventricular (LV) developed pressure, dP/dt and resting pressure were monitored before, and for 2 hours after coronary occlusion. After 90 minutes of regional ischemia, perfluorochemical-treated hearts exhibited significantly greater developed pressure than those perfused with blood (78 +/- 6% versus 61 +/- 5% of preligation values; P less than 0.05). At the end of the experiment, LV dP/dt was 21% greater in the perfluorochemical-perfused group than in the blood-perfused group (74 +/- 8% versus 53 +/- 10%; P less than 0.01). Perfluorochemical perfusion also preserved diastolic function by preventing the 58% increase in left ventricular chamber stiffness (i.e., resting pressure; P less than 0.01) associated with circumflex ligation. Thus, in the present model of regional ischemia, perfluorochemical artificial blood is significantly better than blood at maintaining both systolic and diastolic myocardial function after a major coronary artery has been occluded.

Radionuclide angiography in children

Comment: Although radionuclide angiography is a highly specialized area, we believe that many of our readers will appreciate this very clear exposition of medical progress. By intent, the intricate technical details are omitted; they are available elsewhere. The graceful deletion of most of the fashionable abbreviated (and therefore confounding) terms greatly enhances understanding, to the end that we can easily appreciate both the procedure and its clinical applications.--R.E.M.

Force and oxygen consumption in the immature rabbit heart.

ABSTRACT: We speculated that there are important age-related differences in the economy of left ventricular force development in the isolated heart. To assess this, we evaluated oxygen consumption and force development in newborn (less than 1 wk old) (n = 26), juvenile (4-6 wk old) (n = 26), and adult (5-7 mo old) (n = 26) isolated, isovolumic rabbit hearts. Measurements were obtained with three different interventions, including 1) changes in heart rate, 2) inotropic stimulation with isoproterenol, and 3) changes in end-diastolic pressure. We found no significant baseline differences in the economy of force development. However, when heart rate was increased by 20%, the force/oxygen consumption ratio (economy) increased in newborn hearts by approximately 37%, whereas there was a decrease in juvenile and adult hearts of ∼27%. In addition, with increases in end-diastolic pressure above 10 mm Hg, newborn hearts increased their force/myocardial oxygen consumption ratio to 300% of the baseline value, whereas adults increased to only 160% of baseline. Isoproterenol produced no significant age-related differences in the force/myocardial oxygen consumption ratio. We conclude that there are important age-related differences in the economy of left ventricular force development in this model, but these differences are apparent only at higher heart rates and end-diastolic pressures.

Cardiovascular and respiratory response to static exercise in the newborn kitten

ABSTRACT: Muscle contraction produces a reflex increase in blood pressure, heart rate, and minute ventilation in adults. To evaluate the role of this reflex in newborns, we compared the blood pressure, heart rate, and ventilatory responses to static contraction of the hindlimb muscles in sedated newborn and adult felines. The reflex response to muscle contraction was compared with the baroreflex, the chemoreceptor reflex, and the response to maximal stimulation of sciatic nerve afferents. With muscle contraction, newborn systolic blood pressure increased by 8.5 ± 2.6%, which was significantly less than the adult response of 15.9 ± 1.8% (p < 0.025). Heart rate response to muscle contraction was less in newborns compared with adults, increasing by 1.4 ± 0.5 and 8.3 ± 1.3%, respectively (p < 0.025). In contrast to heart-rate and blood-pressure responses, ventilatory responses to muscle contraction were similar in both age groups, increasing by 34 ± 20 and 34 ± 10% in newborns and adults, respectively. With stimulation of sciatic nerve afferents and with hypoxemia, blood pressure and heart rate increased similarly in both newborns and adults. When the baroreflex was elicited, heart rate decreased similarly in both age groups. We conclude that newborn cats have a reduced heart rate and blood pressure response to muscle contraction compared with the adult. We speculate that the postnatal development of this reflex is due to maturation of integrative and modulatory mechanisms in the CNS.

Milrinone effects in the isolated immature rabbit heart.

Milrinone, a new positive inotropic agent, was evaluated and compared to isoproterenol in an immature isolated isovolumic rabbit heart model. Three age groups were studied: newborns (0-6 days), juveniles (4-6 weeks old) and adults (5-7 months old). Heart rate did not change significantly with milrinone or isoproterenol in adults or juveniles, but increased in newborns from 144 +/- 1 to 162 +/- (SEM) 6 beats/min at peak milrinone effect. Milrinone had a greater effect on the contractility (maximum positive dP/dt) of the mature hearts, with newborns increasing to 134 +/- 6% of baseline, juveniles to 154 +/- 8% and adults to 216 +/- 15%. Results were similar for isoproterenol, although the positive inotropic effect occurred over a wider dosage range for this drug. No additive effects of the two drugs were noted. We conclude, that although milrinone is a positive inotropic drug in all age groups studied, the response of the newborn heart is quantitatively much weaker than that of the adult.

HEMODYNAMIC EFFECTS OF HYDRALAZINE (Hz) IN INFANTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY (CM)

Experience with vasodilator therapy for CM has been limited primarily to adults. Thus, we evaluated the effects of Hz (0.5-1.0 mg/kg IV) during cardiac cath in 13 infants with CM. Ages were 2 to 13 (mean=6.7)months. Each infant had congestive heart failure (CHF) and angiographic evidence of markedly depressed LV ejection fraction (0.24±0.11; mean±1S.D.) with LV dilation (LV end-diastolic volume = 349±125% of normal). Hemodynamic measurements obtained immediately prior to Hz were compared to those taken 30 min after Hz. Results for mean arterial pressure (MAP;mmHg), systemic arteriolar resistance (Rs;units/M2), stroke volume index (SVI;ml/beat/M2)and cardiac index(CI;1/min/M2;by thermodilution)are tabulated below:The 41±14% decrease in Rs was accompanied by a 45±16% increase in CI. Hz increased heart rate (122±19 to 138±18; p<0.001) but this change did not account entirely for the rise in CI, as evidenced by the increase in SVI. Hz also reduced pulmonary resistance and wedge pressure. Oral Hz has been included in the treatment regimen of 10 infants followed for 1 to 38(mean=11) months. Of these, 9 have sustained clinical improvement. We conclude that Hz can be a beneficial adjunct to the management of CHF in young infants with idiopathic dilated cardiomyopathy.