S. Birkeland

Midazolam-fentanyl-isoflurane anaesthesia is suitable for haemodynamic and fluid balance studies in pigs

The domestic pig is a useful model in certain areas of biomedical research. Effective use of this species is often encumbered by lack of reference values in conscious as well as anaesthetized animals. Anaesthesia itself influences physiological and biological variables; the anaesthetic technique often affects experimental results. The relationship between anaesthesia and haemodynamics is well characterized in man, but less established in pigs. We studied the effect of midazolam-fentanyl-isoflurane anaesthesia in six immature, male, domestic pigs (Norwegian landrace). Haemodynamic variables (heart rate, arterial systolic, mean, diastolic pressures, pulmonary systolic, mean, diastolic pressures, pulmonary capillary wedge pressure), tissue perfusion, lymph flow (thoracic duct) were recorded for 3 h in animals with open chest through midline sternotomy. Variables relevant to fluid balance, e.g. interstitial hydrostatic pressure (Pi), serum-colloid osmotic pressure (s-COP) and serum-albumin (s-albumin) and -protein (s-protein) concentrations were measured. With the chosen anaesthetic technique haemodynamic variables, including lymph flow, and laboratory variables remained constant during the study period. Most variables were similar to conditions in humans. In contrast to adult humans exposed to the same anaesthetic technique, these pigs had lower haemoglobin-, s-albumin- and s-protein concentrations. A finding which may reflect immaturity. Liver and lung perfusion decreased significantly during the study period whereas perfusion of the other organs studied remained constant. Lack of responses to defined noxious stimuli during the study period suggest adequate analgesia. We conclude that midazolam, fentanyl and isoflurane provide cardiovascular stability including normal microvascular fluid exchange, which are essential elements for securing the quality of results obtained during cardiovascular research in anaesthetized pigs.

Endogenous Adenosine Attenuates Myocardial Stunning by Antiadrenergic Effects Exerted During Ischemia and Not During Reperfusion

Summary The effect of adenosine receptor blockade and adrenergic blockade on myocardial stunning [left anterior descending coronary artery (LAD) occluded for 10 min and reperfused for 180 min] was studied in 38 open-chest cats. A control group (Control) was compared with two other groups in which adenosine receptors were blocked by 8-phenyltheophylline (7.5 mg/kg) before reperfusion (8-PT-R) or before ischemia (8-PT-I). Group A, in which adrenergic receptors were blocked (doxazosin 200 μg/kg + propranolol I mg/kg), was compared with group A + 8-PT-I, in which both adenosine and adrenergic receptors were blocked before coronary artery occlusion. Regional systolic function assessed by sonomicrometry in the LAD perfused area recovered less in 8-PT-I (55 ± 5% recovery) as compared with Control (87 ± 9%) and 8-PT-R (89 ± 8%), which indicates that adenosine receptor blockade during ischemia increases stunning. Functional recovery was similar in Control, group A (96 ± 5%), and group A + 8-PT-I (87 ± 5%), which demonstrates that if adrenergic receptors are blocked, adenosine receptor blockade during ischemia does not increase stunning. These results may indicate that the cardioprotective effects of endogenous adenosine are mediated through antiadrenergic effects exerted during coronary artery occlusion.

Effects of velocity distribution, diameter measurement and velocity tracing on the accuracy of cardiac output measurement by pulsed Doppler echocardiography in the aortic annulus of pigs.

UNLABELLED The accuracy of cardiac output measurement by pulsed Doppler echocardiography can be affected by several factors, such as the velocity distribution, the measurement of diameter and the method of tracing the pulsed Doppler flow spectrum. This experimental study was designed to find the most accurate way of measuring cardiac output in consideration of all these factors. In 10 open-chest normal piglets (24 +/- 1 kg), the velocity distribution in the aortic annulus was evaluated using Doppler colour flow mapping. Cardiac output was measured by pulsed Doppler echocardiography in the aortic annulus by a number of different ways and compared to the simultaneous result of the thermodilution method. All measurements were made at baseline, after intravenous injection of esmolol and during infusion of dobutamine. RESULTS (1) the velocity distribution in the aortic annulus in the piglets was just slightly skewed during all three haemodynamic situations; (2) The in vivo measurements of the diameter of the aortic annulus varied throughout the ejection period, but the average of the three largest diameter measurements was almost identical with the diameter measured in vitro (18.5 +/- 0.3 mm vs. 18.6 +/- 0.2 mm; p = NS); (3) Tracing the maximal velocity of the pulsed Doppler flow spectrum produced a cardiac output that was 18%-21% higher than that measured by the thermodilution method, while tracing the brightest part (modal velocity) of the pulsed Doppler flow spectrum yielded a cardiac output very close to the thermodilution measurement. CONCLUSION The velocity distribution in the aortic annulus in the piglet has little effect on cardiac output measurement by pulsed Doppler. Using the maximal measurable diameter of the aortic annulus and tracing the brightest part of the pulsed Doppler flow spectrum yielded the cardiac output closest to that measured by the thermodilution method.

Postjunctional α-Adrenergic Stimulation of Inotropy in Hypoperfused Myocardium Outside an Acute Infarct

Summary: The functional significance of myocardial postjunctional α-adrenergic support of inotropy in the vicinity of an acute regional ischemic zone was addressed in pentobarbital-anesthetized, β-adrenergic blocked cats with circumflex coronary artery occlusion. Regional myocardial performance was measured by ultrasonic crystals in the anterior wall perfused by the left anterior descending coronary artery (LAD) before and during postjunctional α-adrenergic antagonism (SK&F 104078 2 mg/kg). A group with unrestricted flow in the LAD (control group) was compared with a group perfused below the autoregulatory pressure range (stenosis group). End-systolic pressure–length relations during dynamic afterload elevation were calculated for assessment of regional contractility. Regional myocardial blood flow (RMBF) was measured by radioactive microspheres. SK&F 104078 did not alter regional myocardial shortening or the slope of end-systolic pressure–length relations in the control group. In the stenosis group, however, α-adrenergic antagonism produced significant deterioration of shortening as well as consistent reduction of the slope of the end-systolic pressure–length relations (p < 0.05). As a reflection of reduced demands for perfusion, impairment of midmyocardial and endocardial blood flow occurred in the stenosis group (p < 0.05). These findings imply a negative inotropic effect of SK&F 104078 in metabolically vasodilated myocardium in the vicinity of an acute ischemic region.

Gradual reduction of coronary perfusion pressure in cats: changes in transmural distribution of blood flow.

We evaluated a model for regional myocardial hypoperfusion in cats with an extracorporeal shunt line to the left main coronary artery, and investigated the effects of reduced coronary perfusion pressure on the transmural distribution of left ventricular blood flow measured with radioactive microspheres. Shunt establishment did not alter cardiac function, myocardial tissue blood flow, or its transmural distribution. An artificial shunt stenosis, which clearly reduced coronary perfusion pressure without changing cardiac function, caused reduced endocardial blood flow, slight flow reduction in mid-myocardium, and no flow change in the epicardium. When a severe stenosis was applied, causing increased end-diastolic pressure and reduced shunt flow, endocardial and mid-myocardial flow further decreased whereas epicardial blood flow remained essentially unchanged. These results demonstrate a transmural profile of the coronary autoregulation capacity.

Negative Inotropic Effect of Propranolol Is Attenuated in Underperfused Feline Heart with an Acute Ischemic Region

Summary β-Adrenergic blockade alleviates myocardial ischemia, probably largely through heart rate (HR) reduction. We hypothesized that the negative inotropic effect of β-blockade, which is believed to be potentially dangerous, is attenuated in underperfused hearts with an acute coronary artery occlusion. We studied the effect of intravenous propranolol (1 mg/kg i.v.) in feline hearts with acute circumflex coronary artery (LCX) occlusion by cross-oriented segments in normally perfused and mildly underperfused left ventricular (LV) anterior wall. A control group (n = 10) was compared with a stenosis group (n = 9) in which the mean coronary perfusion pressure was reduced (91 ± 4 g vs. 136 ± 5 mm Hg, p < 0.01). End-systolic pressure-length (ESP-ESL) relations during dynamic afterload increase and preload reduction were calculated to evaluate regional inotropy. HR and LV peak systolic blood pressure (LVSP) decreased in both groups after β-blockade (p < 0.05). Subendocardial and mid-myocardial blood flow measured by radiolabeled microspheres decreased in the control group (p < 0.05) but was unchanged in the stenosis group. Systolic shortening of circumferential segments also decreased in the control group (p < 0.05) but was unchanged in the stenosis group. ESP-ESL relations of circumferential segments shifted markedly rightward in the control group, whereas a modest rightward shift was noted in the stenosis group. This study in feline heart with acute LCX occlusion showed an attenuated negative inotropic effect of β-blockade in underperfused LV anterior wall