Drop In Systemic Arterial Pressure Research Articles

Clinical progress note: Noncardiac complications in adults with congenital heart disease.

Clinical progress note: Noncardiac complications in adults with congenital heart disease.

Effects of Vasodilation in Heart Failure With Preserved or Reduced Ejection Fraction: Implications of Distinct Pathophysiologies on Response to Therapy

The purpose of this study was to compare hemodynamic responses to vasodilator therapy in patients with heart failure (HF) and preserved ejection fraction (HFpEF) versus HF and reduced ejection fraction (HFrEF). There is no proven therapy for HFpEF. In the absence of data, medicines with established benefit in HFrEF such as vasodilators are frequently prescribed for HFpEF. We compared baseline hemodynamics and acute responses to vasodilation with intravenous sodium nitroprusside in patients with HFrEF (n = 174) and HFpEF (n = 83), determined invasively by cardiac catheterization. Baseline blood pressure, stroke volume, and cardiac output were greater in HFpEF than HFrEF, while pulmonary artery mean and pulmonary wedge pressures were similar. Left ventricular filling pressures were reduced to a similar extent in each group with nitroprusside, but the drop in systemic arterial pressure was 2.6-fold greater in HFpEF (p < 0.0001), and improvements in stroke volume and cardiac output were each ∼60% lower in HFpEF compared to HFrEF (p < 0.0001). Despite similarly elevated filling pressures, HFpEF patients were fourfold more likely than HFrEF to experience a reduction in stroke volume with nitroprusside (p < 0.0001), suggesting greater vulnerability to preload reduction. Pulmonary artery systolic pressure dropped more in HFpEF than in HFrEF despite similar reduction in pulmonary mean pressure and resistance, suggesting higher right ventricular systolic elastance in HFpEF. As compared to patients with HFrEF, patients with HFpEF experience greater blood pressure reduction, less enhancement in cardiac output, and greater likelihood of stroke volume drop with vasodilators. These findings emphasize fundamental differences in the 2 HF phenotypes and suggest that more pathophysiologically targeted therapies are needed for HFpEF.

Efficacy and Safety of Bosentan Treatment for Portopulmonary Hypertension Associated With Syncope

Pulmonary arterial hypertension (PAH) in patients with portal hypertension is also referred to as portopulmonary hypertension (PPHTN). Here, we report a case of PPHTN caused by alcoholic liver cirrhosis in a 43-year-old male who experienced repetitive syncope on exertion. The continuous monitoring of pulmonary artery pressure and radial artery pressure revealed that his PAH was aggravated with a drop in systemic arterial pressure during an exercise test. Bosentan, an endothelin A/B receptor antagonist, improved the patient's hemodynamic parameters and abolished his syncope without adverse effects. This is the first report that bosentan may be effective and safe for PPHTN associated with syncope.

Activation of the Human Complement System by Cholesterol-Rich and PEGylated Liposomes—Modulation of Cholesterol-Rich Liposome-Mediated Complement Activation by Elevated Serum LDL and HDL Levels

Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of “complement activation-related pseudoallergy.” We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since abnormal or racial differences in serum lipid profiles seem to modulate the extent of complement activation and associated adverse responses. In accordance with our earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated human complement, as reflected by a significant rise in serum level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed liposome-mediated SC5b-9 generation considerably. While intravenous injection of cholesterol-rich liposomes into pigs was associated with an immediate circulatory collapse, the drop in systemic arterial pressure following injection of liposomes preincubated with human lipoproteins was slow and extended. Therefore, surface-associated lipoprotein particles (or apolipoproteins) seem to lessen liposome-induced adverse haemodynamic changes, possibly as a consequence of suppressed complement activation in vivo. PEGylated liposomes were also capable of activating the human complement system, and the presence of surface projected methoxypoly(ethylene glycol) chains did not interfere with generation of C3 opsonic fragments. We also show that poly(ethylene glycol) is not responsible for PEGylated liposome-mediated complement activation. The net anionic charge on the phosphate moiety of the phospholipid-mPEG conjugate seemed to play a critical role in activation of both the classical and alternative pathways of the complement system.

Myocardial Energy Metabolism in the Newborn Lamb In Vivo during Pacing-Induced Changes in Oxygen Consumption

Myocardial energy metabolism was studied in newborn sheep to determine whether the metabolic responses to pacing-induced increases in heart rate were similar to those previously found during catecholamine stimulation. Open-chest newborn sheep, 3 to 9 d old (n = 11), underwent atrial pacing at a respiratory rate harmonic just above the intrinsic heart rate. Pacing rate was increased by 30 beats/min every 5 min until conduction block or a drop in systemic arterial pressure occurred. Phosphorous metabolites were monitored simultaneously (n = 7) using a 31P magnetic resonance surface coil over the heart within a magnet operating at 4.7 tesla. Myocardial oxygen consumption was monitoring via an extracorporeal shunt from the coronary sinus. Rate pressure product increased with heart rate and was found to relate to myocardial oxygen consumption (r = 0.75), which increased maximally by 47 +/- 9% due to increases in coronary blood flow. Phosphocreatine/ATP ratio decreased significantly, and calculated ADP increased between baseline and peak performance but returned to near baseline levels during recovery at the initial pacing rate. These findings indicate that intracellular high-energy phosphate concentrations do change with alterations in myocardial oxygen consumption induced by cardiac pacing in the newborn. These changes are similar to those found during epinephrine infusion. Furthermore, the ATP hydrolysis products probably participate in myocardial respiratory regulation in the newborn in vivo.

Hemodynamic Evaluation of Recombinant Human Tumor Necrosis Factor (TNF)-α, TNF-SAM2 and Liposomal TNF-SAM2 in an Anesthetized Dog Model

We have evaluated the hemodynamic effects of systemically administered recombinant human tumor necrosis factor (TNF)-alpha, TNF-SAM2 and liposome-bound TNF-SAM2 in an anesthetized mongrel dog model. A dose of 10 micrograms TNF protein/kg of each formulation was injected in a peripheral vein and mean systemic arterial pressure (SAP), heart rate (HR) and cardiac output (CO) were measured. TNF-alpha induced a marked drop in SAP in all three dogs (mean decrease = 59.3 +/- 5.2 mm Hg; to 61.5% of baseline; p = 0.008); whereas TNF-SAM2 caused a smaller and transient drop in SAP in four dogs (mean decrease = 25.5 +/- 10.1 mm Hg; to 81.2% of baseline; p = 0.086). In three dogs administered liposome-bound TNF-SAM2, which retains antitumor activity in vivo, a net slight hypertensive phase and sustained elevated CO occurred, followed by a return to an essentially normotensive state (101.0% of baseline SAP). This model demonstrates that the principal acute systemic toxicity of TNF, i.e., hypotension, can be markedly attenuated by liposomal formulation of a second-generation TNF.

Coronary Blood Flow Autoregulation and Flow Heterogeneity in the Stunned Heart.

We used an anesthetized swine model of regionally "stunned" myocardium to determine the effect of stunning on coronary autoregulation and blood flow heterogeneity. In 18 domestic swine, stunning was accomplished by reducing blood flow to the left anterior descending coronary artery (LAD) by approximately 75% of baseline for 15 min and restoring it to normal for 1 hour. We quantified coronary autoregulation using both the slope of coronary pressure-flow curves and an autoregulation index. We quantified blood flow heterogeneity using radioactive microspheres to determine the variability in flow (dispersion index) among forty 200 mg segments of myocardium from the center of the stunned, LAD-perfused left ventricle. Before and after stunning, we measured autoregulation, myocardial blood flow and flow heterogeneity, as well as hemodynamic indices of myocardial oxygen demand. Fifteen min of ischemia and 1 hour of reperfusion produced both a 46% reduction in mechanical function, and a 7% drop in systemic arterial pressure, but not change in heart rate or rate pressure product. Myocardial oxygen consumption was 15% reduced and myocardial blood flow 16% reduced in the stunned myocardium when measured at one hour of reperfusion. Fifteen min after reperfusion, the slope of the coronary pressure flow plots and the coronary venous oxygenation were increased whereas the autoregulation index decreased. These findings all indicate reduced autoregulation during early reperfusion. However, after one hour of reperfusion, the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs. 0.48 +/- 0.26 ml.100 g-1.min-1.mmHg-1) and the autoregulation index (0.43 +/- 0.16 vs. 0.30 +/- 0.32) were unchanged from control measurements (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Tidal Volume, FRC, and End-inspiratory Volume in the Development of Pulmonary Edema following Mechanical Ventilation

Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation but does not fundamentally modify the characteristics of this edema which is consistently associated with major permeability alterations. These results may be relevant for ventilatory strategies during acute respiratory failure.

Pulmonary vascular response to endothelin in rats

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pacemaker syndrome in activity-responsive VVI pacing

The “pacemaker syndrome” refers to a wide variety of clinical presentations of intolerance to ventricular pacing ranging from mild light-headedness to frank syncope. 1 These problems are thought to result from the loss of atrioventricular synchrony with consequent loss of the atrial contribution to left ventricular filling, and, in some cases, intact ventriculoatrial conduction with inappropriate atrial-ventricular systole, increased systemic and pulmonary venous pressure and consequent reflex drop in systemic arterial pressure. 2 Some studies have suggested that it is the loss of chronotropic response during VVI pacing that leads to symptoms in many patients; this response can be improved by activity-responsive VVI pacing. 3 We report a case of pacemaker syndrome that resulted from the use of an activity-responsive VVI pacing system.

Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with idiopathic congestive cardiomyopathy, nifedipine enhanced myocardial performance while increasing coronary blood flow and favorably altering the myocardial oxygen supply-demand balance.

The Effect of Prostaglandin E 1 in Patients Undergoing Clinical Cardiopulmonary Bypass

The effect of prostaglandin E 1 (PGE 1) on protection of platelets during cardiopulmonary bypass (CPB) was evaluated in 9 patients, who were compared with an identical control group of 10 patients undergoing coronary artery bypass grafting. To evaluate the hemodynamic side-effects, PGE 1 (0.05 μg/kg/min) was infused prior to CPB, resulting in a 26% drop in mean systemic arterial pressure. With this dose, no inhibition of the adenosine diphosphate-induced aggregation could be measured in the pulmonary artery sample. During CPB, the same infusion dose resulted in a severe drop in systemic arterial pressure below 50 mm Hg in 7 of the 9 patients. In 5 of these patients, volume load and phenylephrine infusion could not compensate for the pressure drop, and PGE 1 had to be reduced to 0.02 μg/kg/min. Platelet aggregation was reduced significantly in the PGE 1-treated group compared with the control group, but not completely inhibited during CPB. However, in the postbypass period no platelet preservation was seen in the PGE 1 group. In both groups, platelet number and function were equally low. No differences were measured in blood loss or blood transfusion requirements. Except for hypotension, no side-effects of the PGE 1 treatment were seen. It is concluded that the hypotension caused by minimal doses of PGE 1 during CPB precluded using higher doses, which might have had a greater effect on platelet inhibition. These hypotensive side-effects should be reduced or eliminated before PGE 1 can be expected to have the same protective effect on platelet damage that has been demonstrated in animal experiments.

EFFECT OF INTRAVENOUS DIAZEPAM ON RENAL FUNCTION

The effect of intravenous diazepam on glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) was investigated in 6 children and 12 anesthetized rabbits. A transient decrease in inulin and PAH clearances was observed in 6 children given 4 mg of diazepam intravenously, without measurable change in blood pressure. A similar renal effect was observed in anesthetized rabbits, together with a transient drop in systemic arterial pressure. Continuous infusion of diazepam (5 mg/kg/hr) did not affect renal function in rabbits. We suggest that this effect of diazepam should be borne in mind when the drug is administered to patients undergoing renal clearance studies or to patients with preexistent renal insufficiency.

Effect of intravenous diazepam on renal function.

The effect of intravenous diazepam on glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) was investigated in 6 children and 12 anesthetized rabbits. A transient decrease in inulin and PAH clearances was observed in 6 children given 4 mg of diazepam intravenously, without measurable change in blood pressure. A similar renal effect was observed in anesthetized rabbits, together with a transient drop in systemic arterial pressure. Continuous infusion of diazepam (5 mg/kg/hr) did not affect renal function in rabbits. We suggest that this effect of diazepam should be borne in mind when the drug is administered to patients undergoing renal clearance studies or to patients with preexistent renal insufficiency.

Effect of the inhibition of angiotensin I converting enzyme in endotoxin and hemorrhagic shock.

SummaryWe studied the role of the angiotensin I converting enzyme in shock Dogs were shocked by injection of E. coli endotoxin or by bleeding. The animals in the experiments were pretreated by iv administration of SQ 20881, the synthetic peptide inhibitor of the converting enzyme. The administration of the inhibitor blocked or attenuated the compensatory rise that followed the initial drop in systemic arterial pressure. In hypovolemic shock, as well, the inhibitor significantly delayed and decreased this compensatory rise in blood pressure. The results indicate that the enzyme has important function in shock.

GENERAL CIRCULATORY ALTERATIONS INDUCED BY INTRAVENOUS INFUSIONS OF SYNTHETIC BRADYKININ IN MAN.

The general hemodynamic effects induced by a continuous intravenous infusion of synthetic bradykinin were studied in ten patients submitted to simultaneous right- and left-heart catheterization. A significant drop in systemic arterial pressure and in total peripheral resistance was observed, coincident with an increase of the cardiac output, heart rate, and stroke volume. There was no consistent change of the pulmonary arterial and left atrial pressures, but the pulmonary vascular resistance decreased significantly.

Effect of an adrenergic blocking agent on vascular alterations associated with endotoxin shock.

The effects of Dibenzyline on the vascular changes associated with endotoxin shock were studied in the dog. Pretreatment with Dibenzyline augmented venous return by decreasing pooling of blood in the liver and probably other areas. The precipitous drop in systemic arterial pressure usually associated with the administration of endotoxin was absent in the Dibenzyline-treated dog, but arterial pressure dropped to the same level as in the nontreated animals within 30 min. Treatment with Dibenzyline had no effect (in 1 hr) on the change in pH, hematocrit, or heart rate.