Model Of Acute Pulmonary Hypertension Research Articles

Adaptation to acute pulmonary hypertension in pigs.

The extent of right ventricular compensation compared to the left ventricle is restricted and varies among individuals, which makes it difficult to define. While establishing a model of acute pulmonary hypertension in pigs we observed two different kinds of compensation in our animals. Looking deeper into the hemodynamic data we tried to delineate why some animals could compensate and others could not. Pulmonary hypertension (mean pressure 45 mmHg) was induced gradually by infusion of a stable thromboxane A2 analogue U46619 in a porcine model (n = 22). Hemodynamic data (pressure‐volume loops, strain‐analysis of echocardiographic data and coronary flow measurements) were evaluated retrospectively for the short‐term right ventricular compensatory mechanisms and limits (Roehl et al. [2012] Acta Anaesthesiol. Scand., 56:449–58) 10 animals showed stable arterial blood pressures, whereas 12 pigs exhibited a significant drop of 16.4 ± 9.9 mmHg. Cardiac output and heart rate were comparable in both groups. In contrast, right ventricular contractility and coronary flow only rose in the stable group. The unchanging values in the decrease group correlated with an increasing ST‐segment depression and a loss of ventricular synchronism and resulted in a larger septum bulging to the right ventricle. Simultaneously, a reduced left‐ventricular end‐diastolic volume and a missing improvement in contractility in the posterior septal and inferior free wall of the left ventricle have been observed. Our findings suggest that right ventricular compensation during acute pulmonary hypertension is strongly dependent on the individual capability to increase coronary flow. The cause for inter‐individual variability could be the dimension and reactivity of the coronary system.

Biocompatibility Assessment of the CentriMag-Novalung Adult ECMO Circuit in a Model of Acute Pulmonary Hypertension

Extracorporeal membrane oxygenation (ECMO) is rarely used in patients with severe pulmonary hypertension (PH) as a bridge to lung transplantation. In this study, we assess the blood biocompatibility of the integrated CentriMag-Novalung ECMO system (venoarterial) in an acute model of PH. Severe PH (≥2/3 systemic) was induced in eight sheep through progressive ligation of the main pulmonary artery. System performance, platelet activation, thromboelastography (TEG) parameters, fibrinogen, plasma-free hemoglobin, and total plasma protein were measured at initiation, 3, and 6 hr of support in the ECMO (N = 4) and sham (N = 4) groups. A stable ECMO flow (2.2 ± 0.1 L/min), low transmembrane pressure gradient, and steady blood O2 and CO2 levels were maintained. Platelet activation was low (<4%) in both the groups, whereas platelet responsiveness to agonist (platelet activating factor) was reduced in the sham group when compared with the ECMO group. There were no differences in the TEG parameters, fibrinogen concentration, plasma-free hemoglobin (<10 mg/dl), and plasma total protein between the two groups. The findings of low levels of platelet activation and plfHb suggest adequate blood biocompatibility of the integrated CentriMag-Novalung circuit use for short-term support in a model of PH.

Beneficial effect of sevoflurane on endotoxin-induced pulmonary hypertension

Pulmonary hypertension (PH) is a life-threatening disease commonly seen in ICU septic patients and associated with poor outcome. New and better therapies are required, since the response to various agents such as NO, prostaglandins and phosphodiesterase inhibitors is usually partial and the mortality rate remains high. Inhaled drugs seem to be an attractive treatment option, since they are delivered directly to pulmonary resistance vessels. A new device (anesthetic conserving device-AnaConDa (ACD)) permitting direct administration of volatile anaesthetics - such as sevoflurane - to the breathing circuit of a conventional ICU ventilator in a safe and effective way has recently been introduced. The aim of the present study was to evaluate the efficacy and safety of sevoflurane administration via the ACD on a porcine model of acute PH during sepsis.

Effects of intravenous diltiazem on a porcine model of endotoxin-induced pulmonary hypertension

Pulmonary hypertension (PAH) is a life-threatening disease commonly seen in ICU septic patients. PAH is characterized by alterations in the pulmonary circulation leading to right ventricular failure and is associated with poor outcome in such patients. Various agents such as nitric oxide, prostaglandins and phosphodiesterase inhibitors have been used for its treatment. Drugs that induce pulmonary vasodilatation, increase contractility and maintain a stable haemodynamic profile seem an attractive treatment option in acute PAH patients. However, there is lack of evidence-based guidelines in the current medical literature. Although oral diltiazem has been shown to improve haemodynamics in chronic PAH patients, it has not been used for the treatment of acute PAH. The aim of the present study was to evaluate the effects of intravenous diltiazem on a porcine model of acute PAH during sepsis.

Tadalafil improves oxygenation in a model of newborn pulmonary hypertension

Sildenafil, a phosphodiesterase-5 inhibitor, significantly improves oxygenation when used in animal models and patients with pulmonary hypertension. Tadalafil is a new and clinically available phosphodiesterase-5 inhibitor that, aside from causing pulmonary vasodilation, has been shown to increase cardiac output in pulmonary hypertensive adults. Its hemodynamic effects on the newborn, however, have not been tested. The objective was to evaluate the effect of tadalafil on central hemodynamics and arterial oxygenation in a piglet model of acute pulmonary hypertension. Laboratory experiment. University laboratory. Seven anesthetized and mechanically ventilated newborn piglets. Pulmonary hypertension was induced and maintained in seven anesthetized and mechanically ventilated newborn piglets following acute exposure to 11% oxygen. The experimental animals received orla tadalafil (1 mg/kg), whereas the control animals were given an equal volume of normal saline. Systemic and pulmonary hemodynamic variables were measured, and the cardiac output and ejection fraction were obtained from two-dimensional echocardiogram and Doppler measurements in all animals. Serial arterial blood gases were also obtained, and the alveolar-arterial oxygen gradient was calculated. In contrast with the control animals, in which no significant changes were noted, in the experimental animals pulmonary arterial pressure decreased on average by 54% and cardiac output increased by 88% following tadalafil administration (p < .05). Tadalafil increased the PaO2 by 48% +/- 21% (p < .01), likely as a result of a 74% +/- 13% reduction in the alveolar-arterial oxygen gradient (p < .01). In a newborn animal model of acute pulmonary hypertension, oral tadalafil administration reduces pulmonary vascular resistance and increases arterial oxygenation by increasing cardiac output and reducing the lung shunt fraction. This previously untested compound deserves additional investigation in laboratory models of persistent pulmonary hypertension of the newborn.

Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension

IntroductionProstacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension.MethodsIn this prospective, randomized, placebo-controlled animal study, twenty-six pigs (mean weight 35 ± 2 kg) were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary artery pressure catheter. The effects of inhaled iloprost (50 μg) were studied in the following groups: animals with acute hypoxia-induced pulmonary hypertension, and healthy animals with and without blockade of the autonomic nervous system.ResultsDuring pulmonary hypertension, inhalation of iloprost resulted in a 51% increase in cardiac output compared with placebo (5.6 ± 0.7 versus 3.7 ± 0.8 l/minute; P = 0.0013), a selective reduction in right ventricular afterload (effective pulmonary arterial elastance: 0.6 ± 0.3 versus 1.2 ± 0.5 mmHg/ml; P = 0.0005) and a significant increase in left ventricular end-diastolic volume (91 ± 12 versus 70 ± 20 ml; P = 0.006). Interestingly, right ventricular contractility was reduced after iloprost-treatment (slope of preload recruitable stroke work: 2.2 ± 0.5 versus 3.4 ± 0.8 mWatt·s/ml; P = 0.0002), whereas ventriculo-vascular coupling remained essentially preserved (ratio of right ventricular end-systolic elastance to effective pulmonary arterial elastance: 0.97 ± 0.33 versus 1.03 ± 0.15). In healthy animals, inhaled iloprost had only minimal haemodynamic effects and produced no direct effects on myocardial contractility, even after pharmacological blockade of the autonomic nervous system.ConclusionsIn animals with acute pulmonary hypertension, inhaled iloprost improved global haemodynamics primarily via selective pulmonary vasodilatation and restoration of left ventricular preload. The reduction in right ventricular afterload is associated with a paradoxical decrease in right ventricular contractility. Our data suggest that this reflects an indirect mechanism by which ventriculo-vascular coupling is maintained at the lowest possible energetic cost. We found no evidence for a direct negative inotropic effect of iloprost.

Effects of inhaled iloprost on right ventriculovascular coupling and ventricular interdependence in acute pulmonary hypertension

Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension (PHT) and right ventricular (RV) failure. Prostacyclins not only affect vasomotor tone, but may also have cyclic adenosine 3',5'-monophosphate-mediated positive inotropic effects and modulate autonomic nervous system (ANS) tone. We studied the role of these different mechanisms in the overall hemodynamic effects produced by iloprost (ILO) inhalation in an experimental model of acute PHT.

Thoracic epidural anesthesia impairs the hemodynamic response to acute pulmonary hypertension by deteriorating right ventricular–pulmonary arterial coupling*

Thoracic epidural anesthesia is increasingly used in critically ill patients. This analgesic technique was shown to decrease left ventricular contractility, but effects on right ventricular function have not been reported. A deterioration of right ventricular performance may be clinically relevant for patients with acute pulmonary hypertension, in which right ventricular function is an important determinant of outcome. In the present study, we tested the hypothesis that thoracic epidural anesthesia decreases right ventricular contractility and limits its capacity to tolerate pulmonary hypertension. Prospective, placebo-controlled study using an established model of acute pulmonary hypertension. University hospital laboratory. A total of 14 pigs (mean weight, 35 +/- 2 kg). After instrumentation with an epidural catheter, biventricular conductance catheters, a pulmonary flow probe, and a high-fidelity pulmonary pressure catheter, seven pigs received thoracic epidural anesthesia and seven pigs served as control. Hemodynamic measurements were performed in baseline conditions and after induction of pulmonary hypertension via hypoxic pulmonary vasoconstriction (Fio2 of 0.15). Ventricular contractility was assessed using load- and heart rate-independent variables. Right ventricular afterload was characterized with instantaneous pressure-flow measurements. In baseline conditions, thoracic epidural anesthesia decreased left but not right ventricular contractility. In untreated animals, pulmonary hypertension was associated with an increase in right ventricular contractility and cardiac output. Pretreatment with thoracic epidural anesthesia completely abolished the positive inotropic response to acute pulmonary hypertension. As a result, ventriculo-vascular coupling between the right ventricle and pulmonary-arterial system deteriorated, and cardiac output was significantly lower in animals with thoracic epidural anesthesia than in untreated controls during hypoxia-induced pulmonary hypertension. Thoracic epidural anesthesia inhibits the native positive inotropic response of the right ventricle to increased afterload and deteriorates the hemodynamic effects of acute pulmonary hypertension.

Endothelin-A receptor blockade and inhaled nitric oxide in a porcine model of meconium aspiration syndrome.

Acute neonatal pulmonary hypertension is associated with increased activation of the endogenous endothelin pathway. We investigated the role of selective endothelin-A receptor blockade using i.v. BQ-123 in a piglet model of meconium aspiration syndrome. Meconium aspiration was induced in 18 anesthetized piglets. Six controls received no further intervention. Six piglets received 1 mg/kg BQ-123 at 120 min, with the addition of 20 ppm inhaled nitric oxide at 240 min. Six commenced nitric oxide therapy at 120 min, and were given i.v. BQ-123 at 240 min. The total study duration was 360 min. Meconium aspiration resulted in acute pulmonary hypertension and elevated endothelin-1 levels in all animals. There were no changes in pulmonary hemodynamics or endothelin-1 levels beyond 120 min in controls. In the group receiving BQ-123 first, this agent alone reduced the pulmonary artery pressure and pulmonary vascular resistance, and the subsequent addition of inhaled nitric oxide further reduced pulmonary artery pressure. In the group first receiving nitric oxide alone, this reduced the pulmonary artery pressure, and the addition of BQ-123 resulted in a fall in pulmonary vascular resistance. Endothelin-1 levels increased with both agents. BQ-123 was found to be a highly effective pulmonary vasodilator and augmented the effects of nitric oxide in this model of acute pulmonary hypertension.

Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension.

Continuous administration of inhaled nitric oxide is now widely used as a potent and selective pulmonary vasodilator. We have evaluated the effects of IV dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)-mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP degradation could augment and prolong the pulmonary vasodilating effects of NO and allow for intermittent NO inhalation. In eight anesthetized and mechanically ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4 min for each concentration and followed by a 10-min NO-free interval after each NO concentration, were evaluated without and with dipyridamole. Pulmonary vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533 +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42 dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05 versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/- 0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%. We conclude that dipyridamole augments the effects of NO on right ventricular afterload, allows for intermittent NO inhalation, and can significantly reduce exposure to NO. IV dipyridamole prolongs the action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO.

Two Aerosolized Nitric Oxide Adducts as Selective Pulmonary Vasodilators for Acute Pulmonary Hypertension

To determine the selective vasodilatory effects of two inhaled "NONOate" aerosols in a closed chest pig model of acute pulmonary hypertension (APH). APH was induced by IV infusion of the prostaglandin H(2)/thromboxane A(2) receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n = 4), dipropylenetriamine NO adduct (DPTA/NO, n = 4) [60 micro mol each], or placebo (n = 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy. Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p < 0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p < 0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO. Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619.

Urodilatin, a natriuretic peptide stimulating particulate guanylate cyclase, and the phosphodiesterase 5 inhibitor dipyridamole attenuate experimental pulmonary hypertension: synergism upon coapplication.

In a model of acute pulmonary hypertension in intact rabbits, we investigated the vasodilatory potency of intravascularly administered urodilatin, a renal natriuretic peptide type A known to stimulate particulate guanylate cyclase. Urodilatin infusion was performed in the absence and presence of the phosphodiesterase (PDE) type 5 inhibitor dipyridamole. Stable pulmonary hypertension was evoked by continuous infusion of the thromboxane mimetic U46619, resulting in approximate doubling of the pulmonary artery pressure (PAP). When infused as sole agents, both urodilatin and dipyridamole dose-dependently attenuated the pulmonary hypertension, with doses for a 20% decrease in PAP being 30 ng/kg min for urodilatin and 10 microg/kg min for dipyridamole. A corresponding decrease in systemic arterial pressure (SAP) was noted to occur in response to both agents. Sequential intravenous administration of a subthreshold dose of dipyridamole (1 microg/kg min), which per se did not affect pulmonary and systemic hemodynamics, and a standard dose of urodilatin (30 ng/kg min) resulted in a significant amplification of both the PAP and the SAP decrease in response to the natriuretic peptide. At the same time, manifold enhanced plasmatic cyclic guanosine monophosphate (cGMP) levels were detected. Aerosolized dipyridamole also dose-dependently attenuated pulmonary hypertension, with only 1 microg/kg min being sufficient for a 20% decrease in PAP, with no SAP decline. Preceding administration of subthreshold aerosolized dipyridamole (50 ng/kg min) did, however, cause only a minor amplification of the pulmonary vasodilatory response to a subsequently infused standard dose of urodilatin. In conclusion, this is the first study to show that urodilatin does possess vasodilatory potency in the pulmonary circulation, and enhanced plasma levels of cGMP and synergy with the PDE5 inhibitor dipyridamole both strongly suggest that this effect proceeds via guanylate cyclase activation. The effect of infused urodilatin is, however, not selective for the pulmonary vasculature, as the systemic vascular resistance declines in a corresponding fashion.

Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension.

Phosphodiesterase type 5 (PDE5) hydrolyzes cyclic guanosine monophosphate in the lung, thereby modulating nitric oxide (NO)/cyclic guanosine monophosphate-mediated pulmonary vasodilation. Inhibitors of PDE5 have been proposed for the treatment of pulmonary hypertension. In this study, we examined the pulmonary and systemic vasodilator properties of sildenafil, a novel selective PDE5 inhibitor, which has been approved for the treatment of erectile dysfunction. In an awake lamb model of acute pulmonary hypertension induced by an intravenous infusion of the thromboxane analog U46619, we measured the effects of 12.5, 25, and 50 mg sildenafil administered via a nasogastric tube on pulmonary and systemic hemodynamics (n = 5). We also compared the effects of sildenafil (n = 7) and zaprinast (n = 5), a second PDE5 inhibitor, on the pulmonary vasodilator effects of 2.5, 10, and 40 parts per million inhaled NO. Finally, we examined the effect of infusing intravenous l-NAME (an inhibitor of endogenous NO production) on pulmonary vasodilation induced by 50 mg sildenafil (n = 6). Cumulative doses of sildenafil (12.5, 25, and 50 mg) decreased the pulmonary artery pressure 21%, 28%, and 42%, respectively, and the pulmonary vascular resistance 19%, 23%, and 45%, respectively. Systemic arterial pressure decreased 12% only after the maximum cumulative sildenafil dose. Neither sildenafil nor zaprinast augmented the ability of inhaled NO to dilate the pulmonary vasculature. Zaprinast, but not sildenafil, markedly prolonged the duration of pulmonary vasodilation after NO inhalation was discontinued. Infusion of l-NAME abolished sildenafil-induced pulmonary vasodilation. Sildenafil is a selective pulmonary vasodilator in an ovine model of acute pulmonary hypertension. Sildenafil induces pulmonary vasodilation via a NO-dependent mechanism. In contrast to zaprinast, sildenafil did not prolong the pulmonary vasodilator action of inhaled NO.

Intraluminal Pulsed Doppler Evaluation of the Pulmonary Artery Velocity Time Curve in a Canine Model of Acute Pulmonary Hypertension

The velocity pattern of the blood flow in the pulmonary artery was investigated in an animal model of acute pulmonary hypertension. Nine anesthetized, open-chest dogs were embolized with polystyrene microspheres, and the velocity pattern of the blood flow in the pulmonary artery was studied with use of an invasive pulsed Doppler technique. Phasic intraluminal velocity was recorded with use of a miniature piezoelectric crystal activated by 20-MHz Doppler pulses and mounted on the tip of a needle probe introduced into the pulmonary artery. The recorded Doppler quadrature signals were processed by spectral analysis. Significant increases occurred in mean, systolic, and diastolic pulmonary arterial pressures (p less than 0.0002), in pulmonary vascular resistance (p less than 0.005), and in negative velocity time (duration in milliseconds that the mean velocity was directed toward the pulmonic valve) (p less than 0.002). Significant decreases occurred in right ventricular ejection time (p less than 0.006) and in positive velocity time (duration in milliseconds that the mean velocity was directed away from the pulmonic valve) (p less than 0.005). A significant shortening in the time to peak velocity (acceleration time) was found (p less than 0.005). Second-order regression analyses demonstrated an inverse correlation between the ratio of positive velocity time to negative velocity time and the mean pulmonary artery pressure in all animals (r = 0.71). These findings should be compared with the velocity patterns of the blood flow in the pulmonary artery obtained under pulmonary hypertensive conditions due to various causes to facilitate interpretation and understanding of clinical investigations.

Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in experimental porcine pulmonary hypertension

We compared the hemodynamic effects of four vasodilators in experimental embolic pulmonary hypertension in a randomized controlled trial, using nine pigs weighing 16 to 23 kg. After anesthesia induction and cannulation with arterial, central venous, and thermodilution output pulmonary artery catheters, animals were repetitively embolized with glass beads (60 to 160 mu) in order to establish pulmonary hypertension (pulmonary artery pressure [PAP] doubled from baseline). Prostaglandin E1 (PGE1), isoproterenol, prostacyclin (PGI2), and nifedipine were compared at doses producing equivalent reduction in systemic BP. Only PGE1 and PGI2 decreased both PAP and pulmonary vascular resistance (PVR). PGE1 decreased PAP from 39 +/- 1 to 33 +/- 1 mm Hg; prostacyclin decreased PAP from 38 +/- 1 to 31 +/- 1 mm Hg and produced the largest increase in cardiac output (Qt). Isoproterenol did not change PAP, markedly increased heart rate (162 +/- 8 to 216 +/- 11 beats/min), and resulted in significant arrhythmias. Nifedipine increased PVR from 1044 +/- 113 to 1125 +/- 100 dyne.sec.cm-5 and decreased Qt. Vasodilators demonstrate unique hemodynamic drug profiles. Isoproterenol infusion is characterized by tachycardia and arrhythmias. Both PGE1 and PGI2 effectively decrease PAP and PVR. Nifedipine depressed Qt significantly in this glass-bead embolization model of acute pulmonary hypertension.

Efficacy of vasodilator therapy in canine model of acute pulmonary hypertension : Priebe H-J: Am J Physiol 255:H1232–H1239, 1988

Efficacy of vasodilator therapy in canine model of acute pulmonary hypertension : Priebe H-J: Am J Physiol 255:H1232–H1239, 1988

Efficacy of vasodilator therapy in canine model of acute pulmonary hypertension.

This study was performed to determine 1) the effects of acute pulmonary embolization (induced by injection of autologous muscle) on right ventricular (RV) performance, coronary hemodynamics, and gas exchange; and 2) the efficacy of subsequent administration of nitroglycerin, prostaglandin E1, and hydralazine with regard to improvement in RV function and gas exchange in eight open-chest dogs. After embolization, pulmonary artery (PA) pressure and vascular resistance (PVR) increased three- to fivefold without changes in RV end-diastolic dimensions (ultrasonic dimension technique) or pressure. However, systolic dimensions increased, and stroke volume (SV) fell. Gas exchange, lung compliance, and pH worsened. Subsequent administration of nitroglycerin (5 micrograms.kg-1.min-1) and prostaglandin E1 (0.2 micrograms.kg-1.min-1) caused further decreases in SV and pH. In contrast, hydralazine (mean 0.15 mg/kg) improved myocardial segment shortening, SV, PVR, pulmonary artery flow, and gas exchange. Coronary blood flow increased by 110%. Thus in this canine model of combined pulmonary hypertension and respiratory insufficiency, nitroglycerin and prostaglandin E1 exerted no beneficial cardiopulmonary effects. In contrast, hydralazine improved regional and global RV performance and gas exchange.

Ventricular interaction in a canine model of acute pulmonary hypertension and its modulation by vasoactive drugs

To determine the effect of a pulmonary glass bead embolism (GBE) upon left ventricular filling, we studied 13 dogs (seven with pericardium open, six with pericardium closed) before and after embolizing the pulmonary artery with sufficient glass beads to triple the pulmonary artery pressure. Furthermore, we examined the nature of the ventricular interaction and the effect upon hemodynamics created by intravenous nitroglycerin, dobutamine and hydralazine. Each dog was implanted with segment length crystals directed in the septal free wall plane of both ventricles, Millar catheters (Millar, Houston) placed in the right ventricle, left ventricle, and pulmonary artery (PA), and a thermodilution catheter placed in the PA. GBE reduced left ventricular end diastolic length (LVEDL) and stroke work, and shifted the left ventricular diastolic pressure-segment relationship (LVDPSR) upwards. The presence of a pericardium had little effect on the biventricular response to any of the test interventions. Nitroglycerin reduced right ventricular end diastolic length (RVEDL) and shifted the LVDPSR downwards. It did not increase LVEDL. Dobutamine increased left ventricular stroke work (LVSW) without altering LVEDL or the LVDPSR. Hydralazine did not change LVEDL, LVSW or shift LVDPSR. We conclude that GBE depresses left ventricular function by the Frank Starling mechanism and shifts the LVDPSR upwards. Because pericardiectomy die not prevent the decrease in LVEDL mediated by GBE, and nitroglycerin did not increase LVEDL despite decreasing RVEDL, a series interaction must dominate.

Effects of Noradrenaline and Isoproterenol on Cardiopulmonary Function in a Canine Model of Acute Pulmonary Hypertension

The authors investigated acute cardiopulmonary effects of noradrenaline and isoproterenol infusion in a canine model of increased pulmonary vascular resistance (PVR) and decreased cardiac output (CO). In six anesthetized, ventilated dogs, autologous blood clots were injected over approximately two hours to increase right ventricular (RV) afterload and decrease CO. After CO had decreased 40 percent dogs were treated with noradrenaline or isoproterenol in alternate sequence. Both drugs increased stroke volume but only isoproterenol affected CO. Flow increased from 1.3 to 3.0 L X min-1 (p less than .01) with isoproterenol infusion. Corresponding to the increase in CO, RV filling pressure and PVR decreased, from 9 to 5 mm Hg, and from 36 to 16 mm Hg X L-1 X min (p less than .01) respectively. When a moderate decrease in CO complicates an acute increase in PVR, isoproterenol may be an excellent drug to treat the decrease in flow.

Ventricular interference.

Ventricular interference.