Partial median sternotomy for repair of heart defects: a cosmetic approach.

A modified median sternotomy incision that results in a cosmetically appealing scar is described. It includes the use of a low-lying short skin incision and partial transection of the sternum. The outcome in 182 infants and children indicates that this approach is safe, provides adequate exposure, and has excellent cosmetic results.

Myosin heavy chain mRNA during the development and regression of myocardial hypertrophy.

RNA synthesis increases during the development and decreases during the regression of pressure-overload induced myocardial hypertrophy. Until now, we have been unable to determine whether these events actually reflected changes in the messenger RNAs for the myosin heavy chain mRNA in the total RNA extracted from rat heart during the development and regression of hypertrophy. We found that the amount of MHC mRNA increased in proportion to the overall increase in total RNA during the development of hypertrophy. However, upon relief of pressure-overload, MHC mRNA decreased to a much greater degree than did total RNA. This is probably related to a sudden cessation of synthesis and the rapid degradation of mRNA. We conclude that the development and regression of myocardial hypertrophy is a function of changes in the mRNA for contractile proteins.

Cation distributions in the hypertrophic myocardium (aortic constriction) of the rat.

Calcium, magnesium, sodium, potassium, and water distributions were determined in rat ventricular muscle during the development of myocardial hypertrophy. Hypertrophy was produced by constriction of the ascending aorta with a silver band. Sham-operated controls were treated similarly, except that the aorta was not constricted. Cation and water distributions were examined at intervals of 1 hour, 1 day, 1 week. Myocardial extracellular space was determined by distribution of [35S] sulphate. In separate experiments, extracellular space was determined in different regions of the normal rat ventricle using [3H] inulin as the extracellular marker. Although some changes were observed in tissue calcium content and the plasma concentrations of several cations, at no time were the cellular concentrations of any cation significantly altered. Myocardial water content and distribution remained nearly constant after constriction of the aorta. Results do not support hypotheses that the heart responds to increased afterload with an accumulation or loss of myocytic calcium sufficiently large to be detectable with standard quantitative methods.

Cardiac involvement in adolescent hypertension. Echocardiographic determination of myocardial hypertrophy.

We measured left ventricular chamber dimension and wall thickness using M-mode echocardiography in 61 adolescents with systolic or diastolic blood pressures above the 90th percentile for age and sex and in 49 normotensive adolescents. Left ventricular posterior wall and ventricular septal thickness indexed to body surface area were significantly greater (p less than 0.001) in the hypertensive group than in the normotensive controls. Left ventricular chamber diastolic and systolic dimensions were not different in the hypertensive group when compared to normotensive adolescents with comparable body size. Left ventricular diastolic and systolic volumes as well as left ventricular function did not differ between the hypertensive and control groups. Calculated parameters of left ventricular hypertrophy, namely, the radius-to-wall-thickness ratio, cross-sectional muscle area, and left ventricular mass, in the hypertensive adolescents were all significantly different (p less than 0.001) from those in the control groups. The finding of myocardial hypertrophy in young, mildly hypertensive subjects suggests early myocardial involvement in the hypertensive process.

Muscle and nonmuscle cell RNA polymerase activities in early myocardial hypertrophy.

RNA polymerase was solubilized from separated rat cardiac muscle and nonmuscle cells during the development of myocardial hypertrophy 1 or 3 days after sham operation or aortic constriction. Six fractions of enzymes designated IA, IB, IIA, IIB, IIIA, and IIIB were identified by DEAE-Sephadex chromatography in each cell population. Fractions designated IA and IB, IIA and IIB, and IIIA and IIIB were similar to RNA polymerase I, II, and III, respectively, found in other eukaryotes. Muscle cell enzyme activity from sham-operated and aortic-constricted rats did not significantly differ 1 day after intervention. By 3 days there was a significant increase in the activity of each enzyme fraction in muscle cells from aortic-constricted rats. There was a slight increase in IIA activity in nonmuscle cells from aortic-constricted rats at 1 day. By 3 days after aortic constriction RNA polymerase IIA, IIB, and IIIB activities increased in nonmuscle cells, but no change was noted in nonmuscle RNA polymerase IA, IB, and IIIA. Changes in RNA polymerase activities in cardiac muscle and nonmuscle cells occur during the development of myocardial hypertrophy but do not appear to correlate with reported changes in RNA synthesis. chromatin-template activity, however, did increase in cardiac muscle cells at both 1 and 3 days after aortic constriction. A similar increase was not seen in nonmuscle cell chromatin-template activity until 3 days. These data suggest that the initial increase in RNA synthesis during the development of myocardial hypertrophy is related to changes in chromatin-template activity in muscle cells. The activities of the RNA polymerase increase after a short delay and vary in their response.

Management of aortic arch interruption with prostaglandin E1 infusion and microporous expanded polytetrafluoroethylene grafts.

Prostaglandin E1 infusion and a microporous expanded polytetrafluoroethylene graft were used in the management of eight infants, all less than 4 days old, with interruption of the aortic arch. Five of the six infants receiving prostaglandin E1 responded dramatically to this therapy, with return of lower limb pulses and lessening of metabolic acidosis. There were no adverse effects attributable to the prostaglandin E1 infusion. Seven infants subsequently underwent aortic reconstruction with a polytetrafluoroethylene graft. There were no operative deaths, and in up to 3 years of follow-up of these patients, graft obstruction occurred in only one patient and this graft was successfully revised. The long-term mortality rate was high (62 percent); all deaths but one were attributable either to the palliation or to the total correction of the associated cardiac malformations.

Hemodynamic response to vascular expansion following immunosympathectomy in spontaneously hypertensive rats.

Spontaneously hypertensive male rats (SHR) or normotensive Kyoto-Wistar (WKY) male rats underwent either sham or nerve growth factor antiserum (NGFAS) treatment during the first week of life. The NGFAS treatment prevented the development of hypertension in SHR but did not prevent the development of left ventricular groups in vivo under general anesthesia. After the recording of resting parameters, homologous whole blood was transfused until the rise in cardiac output reached a plateau. At rest, LV systolic pressure of the NGFAS-treated SHR was significantly lower than that of the sham-treated SHR and not statistically different from that of the WKY rat. The LV end diastolic pressures did not differ among the four groups. Both SHR groups had significantly lower cardiac, stroke, and contractility indices than di the WKY groups. Following vascular expansion, LV filling pressure, stroke index, and stroke work index rose in all groups. The response in the SHR was greater than that in WKY groups. Interestingly, the systolic pressure of the NGFAS-treated SHR rose to the same level as in the sham-treated SHR. Heart rate and calculated systemic vascular resistance fell following transfusion. The SHR appears to exhibit an altered response to increased filling pressure and increased afterload. Our findings are consistent with the concept of an alteration in the compliance of the LV in the SHR.

Effect of a mild exercise program on myocardial function and the development of hypertrophy.

Cardiac function and the development of myocardial hypertrophy were studied in rats conditioned by an exercise program consisting of 8 wk of running on a treadmill. At the end of the training period a group of exercised and sedentary rats was subjected to hemodynamic evaluation under general anesthesia. Except for a slight elevation in the heart rates of the exercised animals there were no significant differences between the exercised and sedentary rats at rest. Following an increase in afterload or a period of hypoxia, the cardiac index of the exercised animals remained significantly higher than that of the sedentary controls. These differences were related to changes in stroke volume. Another group of exercised and sedentary animals underwent either constriction of the ascending aorta or a sham operation. Sedentary rats developed significant hypertrophy at 3 days but had no hypertrophy at 1 day after aortic constriction. Exercised rats, however, developed significant myocardial hypertrophy by 1 day after pressure overload. These data suggest that the heart from an exercised animal is better able to tolerate increases in afterload and hypoxia and can respond with compensatory myocardial hypertrophy more rapidly than the heart of a sedentary animal.

Changes in transcriptional activity during myocardial hypertrophy.

We have demonstrated alterations in the composition of certain groups of nuclear no-histone proteins which could account for the changes in template activity. Further identification of the individual proteins essential for this regulation will aid us in our understanding of the mechanism of myocardial cell growth during hypertrophy. We also have demonstrated the existence of several different RNA polymerase enzymes and have characterized them. The question of de novo synthesis or activation of preexisting enzyme remains unanswered. The delay in changes in activity which we found is also of great interest and may provide information as to the mechanism of increased RNA polymerase activity. The regulation of transcription can occur by changes either in the activity of the chromatin template or in the activities of the various RNA polymerase. Our studies thus far strongly suggest that during the development of hypertrophy both regulatory mechanisms are operative. Furthermore, this appears to be a bimodal function; initially there are changes only in the template and only later do changes in enzyme activity occur. To our knowledge this is the first demonstration of this form of regulation of RNA synthesis in myocardial tissue.

Effect of prophylactic digitalization on the development of myocardial hypertrophy.

The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

Development of left ventricular hypertrophy in young spontaneously hypertensive rats after peripheral sympathectomy.

The effects of peripheral sympathectomy with nerve growth factor antiserum (NGFAS) on blood pressure, systemic hemodynamics, myocardial function, myocardial hypertrophy, and renin were studied in male spontaneously hypertensive (SH) rats of the Okamoto strain and normotensive control Kyoto-Wistar (WKY) rats. NGFAS prevented the developing of hypertension in the SH rats but did not alter blood pressure in the WKY rats. The NGFAS-treated SH rats developed the same hemodynamic abnormalities as the sham-treated rats, including increased peripheral vascular resistance and depressed cardiac output; Indices of left ventricular performance, including peak flow velocity, stroke power, stroke work, dP/dtmax, and flow acceleration (dF/dt), were diminished in the SH rats compared to the WKY rats. NGFAS treatment further depressed ventricular function in the SH rats, but had little effect on the WKY rats; Plasma renin activity in both the SH and WKY rats was unaffected by NGFAS treatment. Although NGFAS treatment effectively prevented the development of hypertension in the SH rats, it did not influence the development of left ventricular hypertrophy as reflected by increases in left ventricular mass, RNA, DNA, and hydroxyproline content. The data suggest that the development of myocardial hypertrophy and myocardial dysfunction in the SH rat is in part independent of hypertension and plasma renin activity.

Heart functional responses to pressure overload in exercised and sedentary rats.

Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function.

Functional evaluation of the rat heart in situ.

We have developed methods for evaluating muscle function in the intact rat heart in situ using a contractility index (dP/dt)P-1, calculated from left ventricular pressure derivative-left ventricular pressure loop plots. Aortic flow measurements were also taken to further characterize in situ rat heart function. The preparation remained functionally stable and was within physiological blood gas and pH limits for at least 30 min following surgical procedures. The contractility index was not influenced by increased afterload, decreased preload or increased heart rate; however, appropriate changes were observed following isoproterenol and propranolol administration. Appropriate changes in aortic flow measurements were observed also with the above interventions. These studies demonstrate that the in situ rat heart is a stable physiological experimental preparation. It should be useful for evaluating heart function since a contractility index derived from pressure-velocity relationships and measurements necessary for pump function analysis can be obtained simultaneously.