Dopamine-dependent diastolic dysfunction in moderate hypothermia.

We designed an experimental animal study to study the effects of dopamine (DA) on diastolic function in hypothermia. DA was applied at five incremental infusion rates in 6 sheep during normothermia and moderate hypothermia (29 degrees C). Left ventricular end-diastolic pressure (LVEDP) was increased during hypothermia as compared with normothermia at all doses of DA. Contraction and relaxation velocity were changed only slightly during hypothermia; during normothermia, both velocities were markedly increased. The pronounced hemodynamic effect observed during hypothermia was further intensified by occurrence of aftercontractions, which disappeared at very high DA doses. These paradoxic results were considered the result of hypothermia-induced reduction in active transport mechanisms responsible for regulation of the cytoplasmic CA2+ concentration. The generally reduced inotropic effect of DA, the risk of paradoxic reactions, and the occurrence of aftercontractions must be taken into account when emergency drugs are administered clinically during hypothermia.

[Ornipressin (POR 8)--effect on coronary blood circulation and the peripheral circulation. An animal experimental study]. / Ornipressin (POR 8)--Wirkung auf die Koronardurchblutung und die periphere Zirkulation. Eine tierexperimentelle Studie.

Ornipressin (POR 8), referred to below as OR, is a synthetic derivative of natural vasopressin. It was introduced into clinical practice to replace epinephrine as a local vasoconstrictor because OR was presumed to produce fewer undesirable side-effects. However, mayor cardiovascular complications following local infiltration of OR have been reported in recent time. Beside increased blood pressure and changes in heart rate, there is evidence that the systemic effects of OR include a distinct vasopressor activity on coronary arteries. This study was planned to investigate the effects of OR in haemodynamics and the coronary vascular system. METHODS. The effects of OR on systemic haemodynamics and coronary circulation were studied in nine anaesthetized closed-chest mongrel dogs. Anaesthesia was administered using N2O/O2 (FiO2:0.33) and enflurane (1.0 vol% endtidal). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a tip catheter manometer. Cardiac output (CO) was determined using thermodilution and coronary sinus blood flow, using a Pitot catheter. Recording of baseline values was followed by bolus injection of OR (0.03 U/kg) and changes in haemodynamics were measured for 90 min at fixed time intervals. Statistical analysis was performed by analysis of variance for repeated measures. A value of P < or = 0.05 was considered to indicate statistical significance. RESULTS. Significant maximum changes occurred within 3-5 min after administration of OR. Systolic and diastolic arterial pressures increased by 33% and 39%, respectively. With only minor changes in heart rate, cardiac output markedly decreased by 44% and total peripheral resistance increased by 159%. Impaired pump function of the left ventricle became obvious by a decrease in maximum dP/dt, a decrease in ejection fraction by 35%, and a concomitant sharp increase in left ventricular enddiastolic pressure by 68% and in endosystolic volume by 41%. At the same time, OR produced a marked impairment of coronary perfusion. Myocardial blood flow fell by 32%, while coronary vascular resistance rose by 112%. Increased myocardial oxygen demand and reduced oxygen supply resulted in very low values of coronary venous oxygen saturation (< 20%). CONCLUSIONS. Systemic effects of OR are characterized by a sharp rise in arterial blood pressure. Concomitantly a decrease of myocardial contractility leads to a compromised left ventricular function with marked increases in left ventricular enddiastolic pressure. These haemodynamic changes are associated with an imbalance of myocardial oxygen demand and delivery due to the distinct OR-induced coronary constriction. With regard to the deterioration of systemic and cardiac haemodynamics the indications and use of ornipressin in clinical practice need to be reevaluated.

Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange.

Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that participates in the regulation of vascular tone. We studied the effects of inhaled NO gas on transient hypoxic pulmonary vasoconstriction and normal lungs in mechanically ventilated sheep. We measured hemodynamics and pulmonary gas exchange. For gas exchange measurements we used conventional blood gas analysis and the multiple inert gas elimination technique to estimate ventilation-perfusion heterogeneity. Our hypotheses were 1) inhaled NO reverses hypoxic pulmonary vasoconstriction, 2) the hemodynamic effects of inhaled NO are limited to the pulmonary circulation, and 3) inhaled NO does not impair pulmonary gas exchange and may redistribute blood flow to better ventilated areas of the lungs. Hypoxic pulmonary vasoconstriction was induced by using a hypoxic inspiratory gas mixture. The addition of 20 ppm NO to the hypoxic inspiratory gases returned pulmonary arterial pressure to baseline values. Systemic hemodynamics and gas exchange indexes derived from conventional blood gas analysis remained constant. Gas exchange indexes for ventilation-perfusion ratios and gas dispersions improved. The addition of 20 ppm NO to medical air (21% O2) had no such significant effects on hemodynamics or pulmonary gas exchange. Our findings show that inhaled NO reverses transient hypoxic pulmonary vasoconstriction. The hemodynamic effects of NO are limited to the pulmonary circulation; it does not impair pulmonary gas exchange. Moreover, it redistributes blood flow to better ventilated alveoli. As such, NO has potential in the treatment of lung diseases associated with pulmonary hypertension.

Right ventricular function assessed by thermodilution technique during apnea and mechanical ventilation.

OBJECTIVES: To evaluate strategies for thermodilution-based measurement of cardiac output and right ventricular (RV) ejection fraction and to assess the effects of controlled mechanical ventilation in patients. Furthermore, to compare strategy-associated reproducibility with reference values obtained during long-term apnea. DESIGN: Crossover trial in patients; reference values from apneic animals. SETTING: University ICU and physiology laboratory. PATIENTS: Six consecutive male ICU patients (48 to 70 yrs) after major abdominal vascular surgery. ANIMALS: two adult female sheep. INTERVENTIONS: Three ventilatory rates (8, 16, and 24 cycles/min) and 15-sec periods of apnea were selected for measurements in patients. In animals, continuous apnea was achieved with extracorporeal CO2 removal and apneic oxygenation. MEASUREMENTS: Measurements were performed using an appropriate pulmonary artery catheter and an ejection fraction/cardiac output computer prototype. The thermal indicator was injected automatically at four defined points of the ventilatory cycle, but triggered manually during apnea. MAIN RESULTS: At 8 cycles/min, there was a wide mean range of cyclic variable modulation, with a coefficient of variation of 11.6% and 23.2% for cardiac output and RV ejection fraction, respectively. Allowing for ventilatory phase or changing from 8 to 16 cycles/min reduced errors by half. Combining both procedures resulted in a coefficient of variation of 4.7% and 6.6% for cardiac output and RV ejection fraction, respectively. The best coefficient of variation values obtained during 15 secs of apnea in patients approached those variations in experimental apnea (coefficient of variation of 2.1% and 4.5% for cardiac output and RV ejection fraction, respectively). CONCLUSIONS: At low ventilatory rates, best results are achieved by averaging four phase-selected measurements. One-point measurements were less accurate and random point measurements less reproducible.

Myocardial contrast echocardiography: cardiovascular effects of the contrast medium SHU 454 in dogs.

SHU 454 (Schering AG, Berlin, Federal Republic of Germany) is a new contrast agent that releases microbubbles with a median diameter of 3 microns into the circulation. During echocardiography, it permits visualization of myocardial blood flow (MBF) when given by intracoronary or aortic root injections. Its hemodynamic effects were investigated in anesthetized dogs with a view to application in humans. Cardiac effects were studied after intracoronary injections of 1 mL of SHU 454 (100 mg/mL). Twenty seconds after injection, MBF increased 35% and coronary vascular resistance decreased accordingly. The increase in MBF was not seen when the coronary bed was maximally dilated with intravenous dipyridamole. Peripheral effects were evaluated after 5 mL of SHU 454 (200 mg/mL) was injected into the aortic root, which gave the same myocardial echo contrast. Aortic pressure decreased 5%, and heart rate and dP/dt increased. To evaluate the effects of hypertonicity, SHU 454 was compared with five radiocontrast media and glucose. Its effects on MBF were similar to those of radiologic contrast media on an equal volume basis. Only 1 mL of intracoronary SHU 454, however, was required for myocardial contrast enhancement. The results suggest that visualization of the myocardium using SHU 454 or similar compounds for contrast echocardiography is a viable prospect.

Evaluation of methods for indirect calorimetry with a ventilated lung model.

A combined lung and ventilator model was built, validated and used to test commercial systems for indirect calorimetry. It simulates O2 uptake and CO2 excretion under ventilator treatment conditions. In the model inspiratory gases are diluted with N2 and CO2 to give the desired expiratory concentrations. Minute volume, FIO2, ventilatory pressure, VO2, VCO2 and consequently RQ can be altered to simulate the adult clinical situation. A selected respiratory pattern is maintained by the lung model. Equipment for indirect calorimetry can then be connected to it and the results compared. Reference values are derived from measurements with a mass spectrometer and a Godart spirometer. Three commercially available instruments (Beckman MMC, Horizon MMC and Engström MC) were evaluated with this system. The limits of agreement with the reference values under different conditions (FIO2 0.4-0.7, ventilatory pressure 0-50 cmH2O) were determined. Differences as high as 15% from the true values of VO2 and V CO2 were observed. The pattern of mechanical ventilation and the intrinsic properties of the analyzers in the equipment used for indirect calorimetry influence measurements to a significant extent.

[Determination of cardiac output under PEEP-respiration with the "NCCOM 3" non-invasive bioimpedence monitor in comparison with the thermodilution method. A study in anesthetized dogs]. / Die Bestimmung des Herzzeitvolumens unter PEEP-Beatmung mit dem nichtinvasiven Bioimpedanzgerät "NCCOM 3" im Vergleich zur Thermodilutionsmethode. Eine Untersuchung an narkotisierten Hunden.

A new noninvasive cardiac output (CO) computer ("NCCOM 3") based on the bioimpedance principle was compared to a CO computer based on standard thermodilution measurements. Simultaneous measurements were made on dogs who were ventilated with or without positive end expiratory pressure (PEEP). There was no correlation of cardiac output measurements with the two methods (r = 0.10, n = 60). Comparing only measurements without PEEP yielded r = 0.41. Thermodilution measurements showed the well-known decline in cardiac output during PEEP, whereas the bioimpedance device recorded an increase in cardiac output. These differences were statistically significant. We conclude that the NCCOM 3 cannot at present replace the invasive standard methods of CO measurement in ventilated patients. A lack of differentiation of circulatory effects, thoracic gas volume, and intrathoracic fluid content is the most likely cause of the discrepancies seen.