Regulation of Cardiac Output with Controlled Heart Rate in Newborn Lambs

Shaddy, Robert E.; Tyndall, Michael; Teitel, David; Li, Carlos; Rudolph, Abraham M.

doi:10.1203/00006450-198811000-00008

Cited by 35 publications

(25 citation statements)

References 22 publications

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“…This shows that in individuals of similar body size, SЈ changes in accordance with PSF, which again is determined by SV, ET, and inotropic state (Table 2), while SЈ and D are expected to change with heart size. The hemodynamic responses to pharmacology and pacing seen in this study are comparable with that of others (31).…”

Section: Discussionsupporting

confidence: 79%

Longitudinal Myocardial Contribution to Peak Systolic Flow and Stroke Volume in the Neonatal Heart

et al. 2011

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Systolic longitudinal myocardial function is important for cardiac ejection. Data describing hemodynamic determinants and the time course of myocardial longitudinal contraction as measured by tissue Doppler are lacking. Ten newborn pigs were used for invasive hemodynamic investigation. Tissue Doppler assessment of the lateral part of the mitral valve annulus during systole was performed during pharmacological modulation of inotropy, cardiac pacing, and modulations of loading conditions. The strongest association was found between peak systolic velocity (SЈ) and peak systolic flow (PSF) and end-systolic pressure (ESP), respectively (␤ ϭ 0.09 cm/mL, p Ͻ 0.001 and ␤ ϭ Ϫ0.07 cm/mL, p ϭ 0.003). Displacement (D) was mostly influenced by stroke volume (SV) (␤ ϭ 0.05 cm/mL, p Ͻ 0.001). Ejection time, SV, ESP, maximum first derivative of pressure (dP/dt max ), and PSF were all associated with SЈ and D under different states of hemodynamic modulation; however, the ratio between PSF and SЈ, SV, and D were stable during hemodynamic modulations. Normalized cross correlations indicate that SЈ and D follow the same trajectory as flow and SV, respectively. In conclusion, this study provides validity of accounting systolic D in the long axis as the longitudinal contribution to SV and peak systolic tissue velocity as the longitudinal contribution to PSF. S ystolic excursion and motion of the mitral valve annulus has been evaluated for myocardial function in both children and adults (1,2). It is easily obtainable in most patients and has the potential of being a routine parameter for assessment of myocardial function (3). Most available data are generated on the basis of studies in adults or experimental data from mature animal studies. In children, data are being published, but validated data explaining changes that occur within and between individuals at all age groups are lacking (4).This study was designed to possibly understand the nature of longitudinal peak systolic velocity (SЈ) and systolic displacement (D) when acting under the influence of hemodynamic changes in small individuals. Neonatal pigs were chosen because of the similarity to human neonates with regards to heart size and heart rate (HR). METHODSPopulation. Ten pigs (age 3-6 d, weight 2520 -6080 g) were studied under general anesthesia. A total of 185 echocardiographic assessments were performed. Twenty (11%) assessments were excluded mainly due to no capture during right atrial pacing, missing data file, or atrial contraction before mitral valve opening during pacing. All animals were in good health without overt clinical signs of disease. The experimental protocol was approved by the Norwegian Animal Research Authority. The animals were cared for and handled in accordance with the European Guidelines for Use of Experimental Animals.Experimental model. The piglets were anesthetized with sevoflurane for i.v. cannulation and maintained on midazolam, fentanyl, and penthobarbital. The animals were mechanically normoventilated (fraction of inhaled oxygen [...

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Section: Discussionsupporting

confidence: 79%

Longitudinal Myocardial Contribution to Peak Systolic Flow and Stroke Volume in the Neonatal Heart

et al. 2011

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“…systemic vascular resistance index; PVRI, pulmonary vascular resistance index. rine dose neonatal heart is very intolerant of increases in afterload and tends to respond to vasoconstriction with a decrease in cardiac output rather than an increase in blood pressure (12). and 2) the tu2-receptor-mediated effects are less evident in the neonatal mammalian pulmonary circulation.…”

Section: Discussionmentioning

confidence: 99%

The Circulatory Effects of Epinephrine Infusion in the Anesthetized Piglet

Barrington

Chan

1993

Pediatr Res

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ABSTRAn. There are few published data regarding the circulatory effects of systemic epinephrine infusions in newborn subjects. We therefore instrumented six piglets aged 5 to 10 d while they were under pentobarbitone anesthesia for determination of cardiac output, left anterior descending coronary artery flow, systemic and pulmonary pressures, and mixed venous, arterial and coronary sinus gases. Systemic, coronary, and pulmonary vascular resistances, coronary oxygen consumption, and myocardial oxygen extraction ratio were calculated. Epinephrine was infused at doses from 0.2 to 3.2 pg/kg/min doubling at 15-min intervals, and measurements were taken after stability had been obtained. Cardiac o u t~u t increased at the lowest dose investigated, i.e. 0.2 pg/kg/min, and progressively increased as the dose was advanced up to 1.6 pglkglrnin, decreasing significantly at 3.2 pg/kg/min. Blood increased progressively, being significantly above baseline at 0.8, 1.6, and 3.2 pg/kg/min and having increased by approximately 81% at the highest dose investigated. Pulmonary arterial pressures were also increased at 1.6 and 3.2 pg/kg/min, but only by 35% at the highest dose of 3.2 pg/kg/min. Systemic and pulmonary vascular resistances both decreased at the three lower doses investigated and then began to increase progressively; however, the systemic vascular resistance increased to a significantly greater degree than pulmonary vascular resistance. Coronary oxygen consumption increased progressively as the epinephrine dose was increased; however, coronary blood flow and coronary oxygen delivery increased more than oxygen consumption, leading to a progressive reduction in myocardial oxygen extraction ratio and a progressive increase in coronary sinus oxygen content. Whole-body oxygen consumption was increased, but to a lesser extent than systemic oxygen transport. We conclude that, at low doses, epinephrine is a potent inotrope and a systemic and pulmonary vasodilator in the newborn piglet. With progressive increases in the dose, systemic vasoconstriction is significantly greater than pulmonary. Increasing cardiac oxygen demands are oversupplied by increases in coronary blood flow. fusions are occasionally used as a back-up inotropic therapy for sick newborn infants (l), particularly those with persistent pulmonary hypertension of the newborn. In such infants, pulmonary vascular resistance is elevated and cardiac output is low (2). A drug that has selective pulmonary vasodilating or selective systemic pressor and positive inotropic properties would therefore be of great value. One previous study of the effects of highdose epinephrine infusions (3.5, 7, and 15 pg/kg/min) (3) in newborn piglets with group B streptococcus-induced pulmonary hypertension suggested a selective systemic pressor effect. To obtain additional information regarding the effects of this mode of therapy, the following study was performed to determine the effects of epinephrine infusions at lower, clinically applicable doses in healthy, acutely instrumented pigle...

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“…3 For an infant SHR, bouts of acute cold exposure that produce hypothermia and bradycardia would necessitate increases in peripheral resistance to maintain arterial blood pressure. 8,10 If the hypothermia and bradycardia were experienced repeatedly, then repeated increases in peripheral resistance during early development could reduce vascular compliance in the adult, perhaps contributing to the development of hypertension. Therefore, thermal factors during development, in addition to a myriad of other physiological, 1 maternal, 2 and dietary factors, 23,24 may contribute to the development of hypertension in SHR.…”

Section: Discussionmentioning

confidence: 99%

“…Because cardiac rate serves as the primary mechanism for the control of cardiac output in infant mammals, 10 bradycardia in response to cooling would be associated with either a drop in arterial pressure or an increase in vascular resistance to maintain pressure. Recordings of arterial pressure from infant rats during cold exposure suggest that the latter possibility is more likely, because blood pressure is maintained at basal levels during both moderate and extreme ambient temperatures.…”

mentioning

confidence: 99%

Thermoregulatory and Cardiac Responses of Infant Spontaneously Hypertensive and Wistar-Kyoto Rats to Cold Exposure

et al. 1999

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Abstract-Cardiovascular function during cold exposure is dependent on effective thermoregulation. This dependence is particularly apparent in infants. For example, we have previously demonstrated that in infant rats during cold exposure, cardiac rate is directly related to their ability to produce heat endogenously. The primary source of endogenous heat production for infant rats is brown adipose tissue (BAT). Because of the dependence of cardiac rate on effective thermoregulation in the cold and because hypertension in spontaneously hypertensive rats (SHR) is influenced by the preweanling environment, in this study we examined the thermoregulatory and cardiac rate responses of infant SHR and Wistar-Kyoto rats (WKY) to varying levels of cold exposure. In experiment 1, 7-to 8-day-old SHR and WKY were acclimated at a thermoneutral air temperature (35°C) and then exposed to successive decreases in ambient temperature (30.5°C, 26.5°C, 23°C, and 17°C) while thermal and metabolic measures were recorded. Although both strains increased BAT thermogenesis and oxygen consumption in response to cold exposure, SHR cooled more than WKY and exhibited lower levels of oxygen consumption at the lowest air temperatures. Experiment 2 was identical to experiment 1 except that cardiac rate was also measured. Again, SHR exhibited substantial thermoregulatory deficits compared with WKY; in addition, they were less able than WKY to maintain cardiac rate at the 2 lowest air temperatures tested. Finally, in experiment 3, infant SHR exhibited diminished BAT thermogenesis in response to a range of doses of a selective ␤ 3 -adrenoceptor agonist. We hypothesize that long-term thermoregulatory deficits during the early postnatal period influence cardiovascular function and contribute to the development of hypertension in SHR. (Hypertension. 1999;33:1465-1469.)Key Words: body temperature regulation Ⅲ brown fat Ⅲ nonshivering thermogenesis Ⅲ heart rate Ⅲ rats, inbred strains Ⅲ hypertension, experimental T he degree of high blood pressure expressed in adult spontaneously hypertensive rats (SHR) is influenced by the neonatal environment. 1-3 Thus, manipulations limited to the preweanling period, such as cross-fostering, 2 pharmacological interventions, 1,4 and handling, 5,6 result in the lowering of blood pressure in adult SHR. Such findings highlight the importance of epigenetic processes in the development of established hypertension in SHR.We have recently demonstrated that thermoregulatory mechanisms play an important role in the protection of cardiovascular function during cold exposure in infant rats. [7][8][9] Specifically, heat produced by brown adipose tissue (BAT) during moderate cold exposure helps to warm cardiac muscle and by doing so contributes to the maintenance of cardiac rate. In contrast, pronounced bradycardia is produced by either extreme air temperatures that overwhelm the ability of BAT to deliver warm blood to cardiac muscle or ganglionic blockade that prevents the activation of BAT thermogenesis in response to the cold.T...

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Regulation of Cardiac Output with Controlled Heart Rate in Newborn Lambs

Cited by 35 publications

References 22 publications

Longitudinal Myocardial Contribution to Peak Systolic Flow and Stroke Volume in the Neonatal Heart

Longitudinal Myocardial Contribution to Peak Systolic Flow and Stroke Volume in the Neonatal Heart

The Circulatory Effects of Epinephrine Infusion in the Anesthetized Piglet

Thermoregulatory and Cardiac Responses of Infant Spontaneously Hypertensive and Wistar-Kyoto Rats to Cold Exposure

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