Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle

2000 ◽  
Vol 279 (6) ◽  
pp. H2975-H2985 ◽  
Author(s):  
Kun Don Yi ◽  
H. Fred Downey ◽  
Xiaoming Bian ◽  
Min Fu ◽  
Robert T. Mallet

Although the β1-adrenergic agent dobutamine is used clinically to provide inotropic support to the failing myocardium, it could jeopardize the myocardium by depleting energy reserves. This investigation delineated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular (RV) myocardium. The right coronary artery (RCA) of anesthetized dogs was cannulated for controlled perfusion with arterial blood, and regional RV contractile function was measured. RCA perfusion pressure was lowered from 100 mmHg baseline to 40 mmHg, and flow fell by 54%. At 15-min hypoperfusion, dobutamine was infused into the RCA at either 0.01 (low-dose dobutamine) or 0.06 μg · kg−1· min−1(high-dose dobutamine) for 15 min. Regional power (systolic segment shortening × isometric developed force × heart rate) stabilized at 63% of baseline during hypoperfusion. Low-dose dobutamine restored power to baseline but did not increase RV myocardial O2consumption (MV˙o2) and thus increased myocardial O2utilization efficiency (O2UE:power/MV˙o2). At 5 min, high-dose dobutamine enhancement of power was similar to that of low-dose dobutamine, but by 15 min, power and O2UE fell to untreated levels. Remarkably, low-dose dobutamine tripled cytosolic phosphorylation potential; in contrast, high-dose dobutamine lowered phosphorylation potential to 45% of the untreated value. Analyses of glucose uptake and glycolytic intermediates revealed sustained enhancement of glycolysis by low-dose dobutamine, but glycolysis became limited at glyceraldehyde 3-phosphate dehydrogenase during high-dose dobutamine treatment. In summary, low-dose dobutamine improved mechanical performance and efficiency of the hypoperfused RV myocardium while increasing myocardial energy reserves, but high-dose dobutamine failed to sustain improved function and depleted energy reserves. Dobutamine is capable of improving both contractile function and cellular energetics in the hypoperfused RV myocardium, but dosage should be carefully selected.

1992 ◽  
Vol 72 (6) ◽  
pp. 2090-2098 ◽  
Author(s):  
G. H. Parsons ◽  
A. C. Villablanca ◽  
J. M. Brock ◽  
R. S. Howard ◽  
S. R. Colbert ◽  
...  

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% “low dose” or 5% “high dose”) before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M P Frick ◽  
S Ostermayer ◽  
S Hamada ◽  
A Kirschfink ◽  
N Marx ◽  
...  

Abstract Objectives Abnormal pulmonary perfusion due to stenosis of the central pulmonary arteries is common after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA). We conducted a monocentric prospective study in young adults after neonatal ASO for TGA to evaluate the effects of abnormal pulmonary perfusion on the increase of the right ventricular stroke volume (RVSV) during dobutamine stress magnetic resonance (DSMR) and on cardiopulmonary exercise capacity. Methods 68 unselected patients (age 18–29 years) underwent CMR at rest and under dobutamine stress (10 to 40 μg/kg/min). RVSV, pulmonary blood flow distribution (PBFD) and peak flow velocity were derived from phase contrast mapping in the main, right and left pulmonary artery (PA) at rest and each stress level. A cardiopulmonary exercise test (CPET) was performed at the same day. All patients reached maximal exercise effort according to heart rate and respiratory exchange rate. Results PBFD at rest: 9/68 patients (13%, ASO-S) had abnormal pulmonary perfusion at rest, defined as PBFD >2:1 (right/left or left/right) and/or relevant stenosis of the main PA (Vmax >2.5 m/s). 59/68 patients (87%, ASO-N) had normal pulmonary perfusion. PBFD under DSMR: (1) In the whole patient group, there was no increase of PBFD under stress compared to PBFD at rest. On an individual patient level, no relevant worsening of abnormal PBFD was found. (2) Under low dose dobutamine, ASO-S had a significantly lower RVSV-increase (RVSVstress/RVSVrest) compared to ASO-N (see figure). However, under high dose dobutamine, this effect was no longer significant (see figure). (3) The RVSV-increase under low and high dose dobutamine did not correlate with peak oxygen uptake during CPET, neither in the total group nor in the subgroups (see table). Peak oxygen uptake was not significantly different between ASO-N and ASO-S (p=0,72). RVSV-increase compared to CPET peak VO2% ASO-total ASO-S ASO-N RVSV-increase/peak VO2% RVSV-increase/peak VO2% RVSV-increase/peak VO2% low dose dobu high dose dobu low dose dobu high dose dobu low dose dobu high dose dobu Pearson correlation coefficient −0.02 −0.05 0.01 −0.22 −0.05 −0.04 p-value 0.90 0.71 0.98 0.56 0.71 0.78 Figure 1 Conclusion (1) Patients with relevant stenosis of main PA and/or abnormal peripheral blood flow distribution (ASO-S) exhibit a reduced RVSV-increase under low dose dobutamine compared to patients without stenosis (ASO-N). This effect was not present under high dose dobutamine stress. (2) These findings did not correlate with peak oxygen uptake during CPET, an objective parameter of cardiopulmonary exercise capacity. (3) Therefore, a conservative proceeding rather than surgery or catheter intervention should be considered, especially in asymptomatic adult patients. Acknowledgement/Funding Supported by Kinderherzen, Fördergemeinschaft Deutsche Kinderherzzentren e.V.


1986 ◽  
Vol 251 (2) ◽  
pp. H364-H373 ◽  
Author(s):  
R. D. Goldfarb ◽  
L. M. Nightingale ◽  
P. Kish ◽  
P. B. Weber ◽  
D. J. Loegering

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.


1990 ◽  
Vol 258 (2) ◽  
pp. H369-H380 ◽  
Author(s):  
B. S. Patel ◽  
M. O. Jeroudi ◽  
P. G. O'Neill ◽  
R. Roberts ◽  
R. Bolli

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) “low-dose” h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) “high-dose” h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.


1998 ◽  
Vol 84 (4) ◽  
pp. 1131-1137 ◽  
Author(s):  
N. Loos ◽  
P. Haouzi ◽  
F. Marchal

Intravenous injection of dopamine (DA) has consistently been shown to depress minute ventilation (V˙e). Whereas at low dosage (≤10 μg/kg) this effect may be accounted for by inhibition of the carotid sinus nerve chemosensory discharge (CSNCD), other mechanisms appear to be involved with large dosage (≥50 μg/kg). The purpose of this study was to elucidate the mechanisms of DA-inducedV˙e depression. The effects of intravenous injection of DA doses ranging from 1 to 200 μg/kg were studied in 18 anesthetized cats. DA was injected during air and O2 breathing, after α-adrenergic blockade by phenoxybenzamine and after baro- and chemodenervation.V˙e and CSNCD were also simultaneously recorded on four occasions. In contrast to that with use of low-dose DA, V˙e depression induced by high-dose DA was dissociated from CSNCD, persisted during 100% O2 breathing, and was significantly correlated with the rise in arterial blood pressure. Although blunted, V˙e depression was still present after complete chemo- and barodenervation but was suppressed by blocking of the concomitant vasoconstriction with phenoxybenzamine. It is concluded that reflexes of circulatory origin contribute to the V˙e depression induced by large-dose DA, in addition to its effects on arterial chemoreceptors. The contribution of baroreceptor stimulation and peripheral vasoconstriction is discussed.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Seong-Hyop Kim ◽  
Chung-Sik Oh ◽  
Tae-Gyoon Yoon ◽  
Min Jeng Cho ◽  
Jung-Hyun Yang ◽  
...  

The study was designed to investigate postoperative nausea and vomiting (PONV) in low- and high-dose remifentanil regimens for total intravenous anaesthesia (TIVA) in adult female patients with American Society of Anaesthesiologists physical status classification I undergoing local breast excision. Propofol and remifentanil 5 ng·mL−1(L group) or 10 ng·mL−1(H group) were administered for anaesthesia induction and maintenance. Propofol was titrated within range of 0.1 μg·mL−1to maintain bispectral index (BIS) values between 40 and 60. Haemodynamic parameters during the intra- and postoperative periods and 24 h postoperative visual analogue scale (VAS) and PONV were evaluated. Each group with 63 patients was analyzed. The H group showed higher use of remifentanil and lower use of propofol, with similar recovery time. Mean systemic arterial blood pressure (MBP), heart rate, and BIS did not differ significantly before and after endotracheal intubation in the H group. However, significant increases in MBP and BIS were apparent in the L group. Postoperative VAS, PONV incidence and scale, and Rhodes index did not differ significantly between the two groups. In conclusion, TIVA with high-dose remifentanil did not aggravate PONV with similar postoperative pain, compared with low-dose remifentanil. Furthermore, high-dose remifentanil showed more haemodynamic stability after endotracheal intubation. This trial is registered withKCT0000185.


Author(s):  
Sarah E. Dyer ◽  
J. David Remer ◽  
Kelsey E. Hannifin ◽  
Aishwarya Hombal ◽  
Joseph C. Wenke ◽  
...  

Extended tourniquet application, often associated with battlefield extremity trauma, can lead to severe ischemia-reperfusion (I/R) injury in skeletal muscle. Particulate oxygen generators (POGs) can be directly injected into tissue to supply oxygen to attenuate the effects of I/R injury in muscle. The goal of this study was to investigate the efficacy of a sodium percarbonate (SPO)-based POG formulation in reducing ischemic damage in a rat hind limb during tourniquet application. Male Lewis rats were anesthetized and underwent tourniquet application for 3 hours, at a pressure of 300 mmHg. Shortly after tourniquet inflation animals received intramuscular injections of either 0.2 mg/mL SPO with catalase (n=6) or 2.0 mg/mL SPO with catalase (n=6) directly into the tibialis anterior (TA) muscle. An additional Tourniquet-Only group (n=12) received no intervention. Functional recovery was monitored using in vivo contractile testing of the hind limb at 1-, 2-, and 4-weeks post-injury. By the 4 week time point, the Low Dose POGs group continued to show improved functional recovery (85% of baseline) compared to the Tourniquet-Only (48%) and High Dose POG (56%) groups. In short, the Low Dose POGs formulation appeared, at least in part, to mitigate the impact of ischemic tissue injury, thus improving contractile function following tourniquet application. Functional improvement correlated with maintenance of larger muscle fiber cross sectional area, and the presence of fewer fibers containing centrally located nuclei. As such, POGs represent a potentially attractive therapeutic solution for addressing I/R injuries associated with extremity trauma.


2005 ◽  
Vol 288 (6) ◽  
pp. H2708-H2714 ◽  
Author(s):  
Ingo Paetsch ◽  
Daniela Föll ◽  
Adam Kaluza ◽  
Roger Luechinger ◽  
Matthias Stuber ◽  
...  

High-dose dobutamine magnetic resonance stress testing has been shown to be superior to dobutamine stress echocardiography for diagnosis of coronary artery disease (CAD). We determined the feasibility of quantitative myocardial tagging during low- and high-dose dobutamine stress and tested the ability of global systolic and diastolic quantitative parameters to identify patients with significant CAD. Twenty-five patients suspected of having significant CAD were examined with a standard high-dose dobutamine/atropine stress magnetic resonance protocol (1.5-T scanner, Philips). All patients underwent invasive coronary angiography as the standard of reference for the presence ( n = 13) or absence ( n = 12) of significant CAD. During low-dose dobutamine stress, systolic (circumferential shortening, systolic rotation, and systolic rotation velocity) and diastolic (velocity of circumferential lengthening and diastolic rotation velocity) parameters changed significantly in patients without CAD (all P < 0.05 vs. rest) but not in patients with CAD. Identification of patients without and with CAD during low-dose stress was possible using the diastolic parameter of “time to peak untwist.” At high-dose stress, none of the global systolic or diastolic parameters showed the potential to identify the presence of significant CAD. With myocardial tagging, a quantitative analysis of systolic and diastolic function was feasible during low- and high-dose dobutamine stress. In our study, the diastolic parameter of time to peak untwist as assessed during low-dose dobutamine stress was the most promising global parameter for identification of patients with significant CAD. Thus quantitative myocardial tagging may become a tool that reduces the need for high-dose dobutamine stress.


1997 ◽  
Vol 16 (6) ◽  
pp. 327-333 ◽  
Author(s):  
Mohamed Alaa A Omran ◽  
Ismail M Abdel-Nabi

1 The effect of Egyptian cobra (Naja haje) venom on the normal electrical activity of the cardiac muscles (ECG) and arterial blood pressure of envenomated rats were investigated in this study. 2 Rats were divided into three groups. The first group was injected im with saline and considered as control group. Rats of the second and third groups were injected IM with 0.02 μg and 0.04 μg cobra venom/ gim b.wt, respectively. 3 Mean blood pressure (MBP), heart rate (HR) and four different ECG parameters (PR and QT intervals, R and T wave amplitudes) were measured over 1 h following envenomation. 4 The low dose (0.02 μg/g) of N. haje venom caused hypotension accompanied by an increase in the HR, whereas hypertension and bradycardia developed after injection of the high dose (0.04 μg/g) of venom. 5 There was a decrease in the P-R interval after administration of the low dose and prolongation of it after the high dose. The Q-T interval and R-wave amplitude were significantly increased after injection of both doses. T-wave amplitude was significantly elevated only after injection of the high dose. 6 The present results indicate that the Egyptian cobra (N. haje) venom significantly alters the arterial blood pressure and ECG parameters of envenomated rats. This suggests that impairment of the electrical activity of cardiac muscle may be one of the reasons why victims of cobra bite die.


1990 ◽  
Vol 259 (3) ◽  
pp. H889-H901 ◽  
Author(s):  
M. O. Jeroudi ◽  
F. J. Triana ◽  
B. S. Patel ◽  
R. Bolli

Controversy persists regarding which oxygen metabolites are cytotoxic. Although the combination of superoxide dismutase (SOD) and catalase has been shown to attenuate postischemic myocardial dysfunction ("stunning"), it is unknown whether this beneficial effect is due to scavenging of O2-., H2O2, or both. Accordingly, 85 open-chest dogs underwent a 15-min occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. In phase A, dogs received an intravenous infusion of saline (group I), SOD (5 mg/kg, group II), catalase (12,000 U/kg, group III), or the combination of SOD and catalase (same doses, group IV). Recovery of regional myocardial function (assessed as systolic wall thickening) after reperfusion was significantly improved by the combination of SOD and catalase but not by SOD alone or catalase alone. To determine whether higher doses of enzymes are more effective, in phase B dogs received an intracoronary infusion of normal saline (group V), SOD in low dose (1.5 mg/kg, group VI), SOD in high dose (6.3 mg/kg plus 1.5 mg/kg iv, group VII), catalase in low dose (18,000 U/kg, group VIII), or catalase in high dose (240,000 U/kg plus 40,000 U/kg iv, group IX). Despite the fact that the local plasma levels of enzymes were considerably higher than those achieved in phase A, none of the treatments in phase B significantly enhanced recovery of contractile function. This study demonstrates that the combination of SOD and catalase is more effective than either enzyme alone in attenuating postischemic myocardial dysfunction and that increasing the doses of SOD or catalase does not provide additional protection. The results suggest that both O2-. and H2O2 contribute significantly to the pathogenesis of myocardial stunning after regional ischemia in the intact animal. Furthermore, the data imply that if SOD and catalase are to be used clinically to prevent postischemic dysfunction, protection may be achieved most effectively by combining the two enzymes.


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