Superior mesenteric blood flow during experimentally induced dumping in man.

The superior mesenteric circulation was studied with a dye-dilution technique after catheterization of the superior mesenteric artery and vein during provoked dumping in 5 patients. Dumping was provoked by intrajejunal instillation of 150 ml 50% glucose. A marked increase of, on the average, 157% was recorded in the superior mesenteric blood flow within a few minutes of the installation of glucose. The maximal increase in the flow was, on the average, 223% and occurred about 40 minutes after provocation. The instillation of glucose was promptly followed by a reduction in vascular resistance of the superior mesenteric vessels by 63% which decreased further to a mean maximal reduction of 76% below the resting level. The increase in the ratio between the superior mesenteric blood flow and cardiac output from 12 to 27% following instillation of glucose further underlines the pronounced vasodilatation of the small intestine. Superior mesenteric angiography at different intervals after provocation of dumping showed that the increased superior mesenteric blood flow is due to a local increase in the flow.     

Effects of vasopressin on cardiac output and its distribution in the subhuman primate

The effects of vasopressin, when administered as intravenous bolus injections and infusions, on cardiac output and the distribution of blood flow to the splanchnic vascular beds were studied in six anesthetized rhesus monkeys. Vasopressin as bolus injections caused dose-dependent decreases in superior mesenteric arterial blood flow. However, small reductions in cardiac output were observed only at the highest doses concomitant with increases in systemic arterial pressure. When vasopressin was infused at the highest dose (5 X 10(-2) units kg-1 min-1) for 10 minutes, cardiac output was unaffected; but sustained reductions in superior mesenteric arterial blood flow and increases in arterial pressure and total peripheral resistance were observed. Infusions of vasopressin (5 X 10(-3) units kg-1 min-1) caused significant and sustained reductions in superior mesenteric arterial blood flow and increases in arterial pressure but no measurable effects on cardiac output or total peripheral resistance. However, there was a significant redistribution of blood flow away from the stomach, small and large intestines, spleen, and pancreas toward the liver (hepatic artery), with no statistically significant change in renal blood flow. On the assumption that comparable responses exist among primates, these data support the clinical use of vasopressin to control gastrointestinal hemorrhage and to offer a probably ideal dose and route of administration.     

Initial management of severe hemorrhage with an oxygen-carrying hypertonic saline solution

We tested the hypothesis that the combination of polymerized bovine hemoglobin (PBHg) with hypertonic saline may be beneficial for the initial management of hemorrhagic shock in 22 mongrel dogs (15 +/- 1 kg) bled to a mean arterial pressure (MAP) of 40 mm Hg in 5 min and maintained at this level for 45 min (shed blood volume approximately 50 ml/kg). Animals were treated with a 4 ml/kg bolus over 4 min of one of the following fluids: whole blood, 7.5% NaCl (HS), 13 g/dl of PBHg, or 7.5% NaCl combined with polymerized bovine hemoglobin (HS-PBHg). No additional intervention was performed, and the animals were followed for 60 min after treatment. PBHg and HS-PBHg produced a sustained, significant increase in MAP. Cardiac output was transiently increased only after HS and HS-PBHg. A partial increase in superior mesenteric artery blood flow was observed, particularly after HS-PBHg. We concluded that small volumes of PBHg alone restore MAP, but not blood flow. The combination of PBHg with hypertonic saline provides improvements in cardiac output and mesenteric blood flow, suggesting a potential benefit for the initial management of major blood loss.     

Effects of sympathomimetic and sympatholytic agents on mesenteric hemodynamics in hemorrhagic hypotension

Hemodynamic effects of sympathomimetic and sympatholytic agents on mesenteric circulation both before and after hemorhage have been studied in anesthetized dogs. By acute hemorrhage of 25.8 ml per Kg of body weight, 82 per cent decrease in superior mesenteric artery flow was noted, while cardiac output decreased by 69 per cent. Mesenteric vascular resistance increased by 97 per cent, whereas total peripheral vascular resistance increased by 27 per cent. Administration of norepinephrine resulted in a diphasic, response of superior mesenteric artery flow in controls, i.e., the initial flow decrease was followed by the subsequent increase. However, a number of animals in hemorrhagic hypotension did not show the diphasic flow response because of the lowered response to catecholamines. The hemodynamic changes induced by epinephrine were similar to those by norepinephrine. However, in the initial flow decrease noted following epinephrine adminsstration was less than that of norepinephrine. Administration of isoproterenol resulted in a marked increase (p<0.05) of superior mesenteric artery flow and of cardiac output even in hemorrhagic hypotensive state. By phenoxybenzamine administration superior mesenteric artery flow was significantly (p<0.05) increased in controls, whereas the flow was greatly decreased in several hypotensive animals. Propranolol produced a significant reduction (p<0.05) in cardiac output and a secondary decrease in superior mesenteric artery flow both before and after he morrhage.     

Redistribution of Microcirculatory Blood Flow within the Intestinal Wall during Sepsis and General Anesthesia

Background: Hypoperfusion of the intestinal mucosa remains an important clinical problem during sepsis. Impairment of the autoregulation of microcirculatory blood flow in the intestinal tract has been suggested to play an important role in the development of multiple organ failure during sepsis and surgery. The authors studied microcirculatory blood flow in the gastrointestinal tract in anesthetized subjects during early septic shock.

Methods: Eighteen pigs were intravenously anesthetized and mechanically ventilated. Regional blood flow in the superior mesenteric artery was measured with ultrasound transit time flowmetry. Microcirculatory blood flow was continuously measured with a six-channel laser Doppler flowmetry system in the mucosa and the muscularis of the stomach, jejunum, and colon. Eleven pigs were assigned to the sepsis group, while seven animal served as sham controls. Sepsis was induced with fecal peritonitis, and intravenous fluids were administered after 240 min of sepsis to alter hypodynamic sepsis to hyperdynamic sepsis.

Results: In the control group, all monitored flow data remained stable throughout the study. During the hypodynamic phase of sepsis, cardiac output, superior mesenteric artery flow, and microcirculatory blood flow in the gastric mucosa decreased by 45%, 51%, and 40%, respectively, compared to baseline (P < 0.01 in all). Microcirculatory blood flow in the muscularis of the stomach, jejunum, and colon decreased by 55%, 64%, and 70%, respectively (P < 0.001 in all). In contrast, flow in the jejunal and colonic mucosa remained virtually unchanged. During the hyperdynamic phase of sepsis, there was a threefold increase in cardiac output and superior mesenteric artery flow. Blood flow in the gastric, jejunal, and colonic mucosa also increased (22%, 24%, and 31% above baseline, respectively). Flow in the muscularis of the stomach returned to baseline, while in the jejunum and colon, flow in the muscularis remained significantly below baseline (55% and 45%, respectively, P < 0.01).     

Dose-related effects of isoflurane on superior mesenteric vasoconstriction induced by endotoxemia in the rat

To investigate the interplay between endotoxin-induced circulatory shock and the cardiovascular effects of different doses of isoflurane, mean aortic pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), heart rate (HR), cardiac output and superior mesenteric artery flow (SMAF), were monitored in rats anesthetized with either 1.4% or 2.0% isoflurane in oxygen. Cardiac index (Cl), total peripheral vascular resistance (TPR) and superior mesenteric vascular resistance (SMVR) were derived. During continuous administration of isoflurane, endotoxin (LD90, 40 mg X kg-1 iv) was given after a 30-min baseline period, and data were collected for an additional 2-h period. Sham-challenged (saline) animals served as controls. The response to endotoxin in the systemic circulation showed a decrease in Cl and MAP, while HR and TPR increased. MPAP and CVP were essentially unchanged. There were no significant differences in the systemic circulation variables between endotoxin groups, apart from a more pronounced HR increase during 1.4% isoflurane. Regionally, however, SMAF was lower and SMVR was higher in the 2.0% versus the 1.4% isoflurane group following endotoxin. To conclude, the degree of mesenteric vasoconstriction during endotoxemia was dependent on the dose of isoflurane. This dose-related effect seems to be mediated through interaction with intrinsic vascular control, a higher dose allowing a more pronounced local blood flow reduction.     

Measurement of mesenteric blood flow by duplex scanning

Ultrasonic imaging combined with a pulsed Doppler unit (duplex scanning) allows the noninvasive assessment of blood flow of the superior mesenteric artery. The changes in mesenteric blood flow associated with a standardized (1000 kcal) food load were measured and the results were compared with blood flow of the left common carotid artery. Twenty healthy subjects (aged 30.1 +/- 5 years) were studied fasting (12.4 +/- 2.6 hours' duration) and six times with a 15-minute interval after the test meal. The diameters of the superior mesenteric artery (0.60 +/- 0.09 mm) and of the common carotid artery (0.61 +/- 0.05 mm) were measured from the B-mode image. The Doppler frequency spectra were used to determine peak systolic, late systolic, and end-diastolic velocity and to compute the mean velocity. Although the flow parameters of the common carotid artery were virtually unaffected by food intake, a steep increase in mesenteric blood flow velocity and volume flow was observed. At rest, blood flow through the mesenteric artery was 6.3 +/- 2.6 ml/sec and 9.5 +/- 2.1 ml/sec in the carotid artery. After the test meal, mesenteric artery blood flow increased significantly (p less than 0.0001) and reached maximal hyperemia (20.3 +/- 7.4 ml/sec) after 45 minutes. The measurement of mesenteric blood flow before and after a test meal characterizes intestinal hemodynamics and should be suitable to evaluate ischemic disease and other disorders that lead to changes of mesenteric blood flow.     

Effect of physical exercise on internal carotid artery blood flow after arterial reconstruction.

The effect of physical exercise on internal carotid artery (ICA) blood flow in conscious man was studied with the aid of electromagnetic flowmetry. A flow probe was implanted on the ICA in 25 patients after reconstruction of the artery. ICA mean blood flow and brachial artery mean blood pressure were continuously monitored in supine (25 patients) and sitting (24 patients) position at rest, during 5-6 minutes exercise on a bicycle ergometer and at rest after exercise. Arterial carbon dioxide tension (PaCO2) was studied in 6/25 work tests in supine and 7/24 in sitting position. Cardiac output was measured at rest and during exercise in 10/25 patients in supine and 8/24 patients in sitting position. In the supine group, ICA flow increased significantly within 1 minute and reached a maximal flow 15% above control flow within 2 minutes after the onset of exercise. The ICA flow then gradually declined, but remained almost significantly elevated, 7.5% above control, on termination of exercise. At rest, after exercise, the ICA flow decreased almost significantly to a level of 5% below the control flow within 5 minutes. There was a significant PaCO2 increase of 2.6 mmHg during exercise and a highly significant increase (72%) in cardiac output during exercise. The ICA flow at rest, before exercise, was about 15% lower in the sitting group than in the supine group. It increased in average 11.5% with 2 minutes of exercise and then gradually diminished. At rest, after exercise, ICA flow decreased further to a level of 8% below control flow within 5 minutes. PaCO2 increased significantly in average 1.6 mmHg during exercise. Cardiac output increased highly significantly (85%) during exercise. The ICA flow changes obtained during exercise in the present study indicate the presence of a regulatory mechanism counteracting the increasing perfusion pressure, but it is unable to compensate the decreased perfusion pressure when the body position was altered from supine to sitting. The cerebral vascular bed in the present patient material seems to operate above and below the lower limit of its pressure range for an adequate autoregulation.     

Measurement of portal blood flow in man by a continuous local thermodilution method. III. Effects of dopamine on systemic and portal hemodynamics after hepatectomy

We gave dopamine (3 micrograms/kg/min, 30 min) intravenously on the third day after hepatectomy to 19 patients, and studied the effects of the drug on systemic and portal hemodynamics. In another 42 patients, administration of dopamine at the same rate was started soon after hepatectomy and continued for about 2 weeks; the clinical results were evaluated. After hepatectomy, the systemic hemodynamics were hyperdynamic and the portal hemodynamics were hypodynamic. After 30 min of dopamine administration, the oxygen pressure in portal blood increased, and because portal blood flow also increased, the oxygen delivery to the liver increased. The mechanism involved an increased proportion of portal venous flow to cardiac output, and a decrease in the splanchnic resistance, not portal venous resistance. Probably, specific dopamine receptors played important role in the increase in the superior mesenteric arterial blood flow. Among 42 patients given small dosage of dopamine, the clinical symptoms of five of seven who had developed liver failure improved. None of the other 35 patients given dopamine preventively developed liver failure. Dopamine in small doses is useful for the management of liver failure after liver resection.     

Effects of dopamine, dobutamine, and dopexamine on microcirculatory blood flow in the gastrointestinal tract during sepsis and anesthesia

BACKGROUND: Insufficient blood flow to the splanchnic organs is believed to be an important contributory factor for the development of organ failure after septic shock. It has been suggested that increasing systemic flow also may improve splanchnic blood flow in septic patients. The aim of this study was to compare the effects of three commonly used inotropic agents, dopamine, dobutamine, and dopexamine, on systemic (cardiac index), regional (superior mesenteric artery), and local (micro-circulatory) blood flow during septic shock in pigs. METHODS: Eight pigs were intravenously anesthetized, mechanically ventilated, and exposed to sepsis induced by fecal peritonitis. Cardiac index was measured with thermodilution, superior mesenteric artery flow was measured with ultrasound transit time flowmetry, and microcirculatory blood flow was continuously measured with a six-channel laser Doppler flowmetry in the gastric, jejunal, and colon mucosa as well as in the kidney, pancreas, and jejunal muscularis. Each animal received, in a random-order, crossover design, the three test drugs, one at a time: 5 and 10 microg x kg(-1) x min(-1) dopamine, 5 and 10 microg x kg(-1) x min(-1) dobutamine, and 1 and 2 microg x kg(-1) x min(-1) dopexamine. Administration of each drug at each dose continued for 30 min and was followed by a 40- to 60-min recovery period. A new baseline was taken before the next drug was administered. RESULTS: All three drugs significantly increased cardiac index; dopamine by 18%, dobutamine by 48%, and dopexamine by 35%, compared with baseline (P < 0.001 for each). At the same time, superior mesenteric artery flow increased by 33% (P < 0.01) with dopamine and 13% (P < 0.01) with dopexamine, whereas it did not change with dobutamine. Microcirculatory blood flow did not change significantly in any of the organs studied with any of the drugs tested. CONCLUSION: All the inotropic agents markedly increased cardiac output in this sepsis model. However, increased systemic flow did not reach the microcirculation in the gastrointestinal tract. This may in part explain why some of the clinical trials, in which systemic oxygen delivery was deliberately increased by administration of inotropic drugs, have failed to improve survival in critically ill patients.     

Redistribution of microcirculatory blood flow within the intestinal wall during sepsis and general anesthesia

BACKGROUND: Hypoperfusion of the intestinal mucosa remains an important clinical problem during sepsis. Impairment of the autoregulation of microcirculatory blood flow in the intestinal tract has been suggested to play an important role in the development of multiple organ failure during sepsis and surgery. The authors studied microcirculatory blood flow in the gastrointestinal tract in anesthetized subjects during early septic shock. METHODS: Eighteen pigs were intravenously anesthetized and mechanically ventilated. Regional blood flow in the superior mesenteric artery was measured with ultrasound transit time flowmetry. Microcirculatory blood flow was continuously measured with a six-channel laser Doppler flowmetry system in the mucosa and the muscularis of the stomach, jejunum, and colon. Eleven pigs were assigned to the sepsis group, while seven animal served as sham controls. Sepsis was induced with fecal peritonitis, and intravenous fluids were administered after 240 min of sepsis to alter hypodynamic sepsis to hyperdynamic sepsis. RESULTS: In the control group, all monitored flow data remained stable throughout the study. During the hypodynamic phase of sepsis, cardiac output, superior mesenteric artery flow, and microcirculatory blood flow in the gastric mucosa decreased by 45%, 51%, and 40%, respectively, compared to baseline (P < 0.01 in all). Microcirculatory blood flow in the muscularis of the stomach, jejunum, and colon decreased by 55%, 64%, and 70%, respectively (P < 0.001 in all). In contrast, flow in the jejunal and colonic mucosa remained virtually unchanged. During the hyperdynamic phase of sepsis, there was a threefold increase in cardiac output and superior mesenteric artery flow. Blood flow in the gastric, jejunal, and colonic mucosa also increased (22%, 24%, and 31% above baseline, respectively). Flow in the muscularis of the stomach returned to baseline, while in the jejunum and colon, flow in the muscularis remained significantly below baseline (55% and 45%, respectively, P< 0.01). CONCLUSIONS: It appears that in early septic shock, autoregulation of microcirculatory blood flow is largely intact in the intestinal mucosa in anesthetized pigs, explaining why microcirculatory blood flow remained virtually unchanged. This may be facilitated through redistribution of flow within the intestinal wall, from the muscularis toward the mucosa.     

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.     

Physiologic effects of transfusing red blood cells with high or low affinity for oxygen to passively hyperventilated, anemic baboons: systemic and cerebral oxygen extraction.

Anemic, passively hyperventilated baboons were given preserved red blood cells either with increased or with slightly reduced affinity for oxygen to restore the red cell volume. In the high affinity group there was a 50% increase in cerebral blood flow immediately after the transfusion, but there was no significant change in the low affinity group. The cardiac output decreased slightly in the low affinity group, and increased slightly but insignificantly in the high affinity group. Two hours after transfusion the cerebral blood flow had returned to normal in the high affinity group. In both groups there was a decrease in arterial blood pH and an increase in Po2 in blood from the pulmonary artery and the jugular vein after transfusion. A 40% restoration of the 2,3 DPG level occurred within 4 hours of the transfusion of red cells with high affinity for oxygen, and this rapid increase was associated with increases in blood pH and inorganic phosphorus levels. Preserved red cells with high affinity for oxygen and low 2, 3 DPG levels significantly increased the cerebral circulation during the 2-hour posttransfusion period. These findings lend support to the recommendation that preserved red cells with normal or elevated 2,3 DPG levels be administered to patients in hemorrhagic or septic shock, and to patients subjected to extracorporeal circulation during cardiac surgery in order to lessen the demand for increased blood flow and to ensure adequate tissue oxygenation during the postoperative period.     

Changes in splanchnic blood flow and cardiovascular effects following peritoneal insufflation of carbon dioxide

Summary Laparoscopic surgery has rapidly become a popular and widely used technique. Although this procedure has been shown to be generally safe, cardiovascular derangement related to carbon dioxide pneumoperitoneum has been reported. There are few data available on the relationship between systemic and regional hemodynamics in cases of pneumoperitoneum. Changes in splanchnic blood flow and cardiovascular effects following a moderate increase of intraabdominal pressure (IAP) to 16 mmHg during a 3-h period were analyzed in six anesthetized dogs. After insufflation, cardiac output and blood flow in the superior mesenteric artery and portal vein decreased progressively and returned to the preinsufflation values following deflation. Hepatic arterial blood flow did not change significantly, perhaps due to compensatory mechanisms for maintenance of hepatic blood flow. Mechanical compression of the splanchnic capillary beds due to the elevated IAP may possibly reflect the increase in systemic vascular resistance causing the decrease in cardiac output. To prevent this impairment, intermittent decompression of gas during surgical laparoscopy is recommended.     

The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients

Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short-term, insulin-dependent diabetic patients. The measurements were performed twice within 2 wk, in random order. Continuous subcutaneous insulin infusion (CSII) was applied for 1 wk in order to obtain good control. All eight patients had elevated cardiac output (median 9%) and forearm blood flow (median 34%) during poor compared with good metabolic control, P less than 0.01. In contrast, hepato-splanchnic blood flow was lower (median 12%) during poor compared with good metabolic control, P less than 0.05. Heart rate remained unchanged, while mean arterial blood pressure was slightly higher during poor control, P less than 0.05. Five of six patients had elevated plasma noradrenaline concentration during poor metabolic control. Due to the small number of patients investigated, no valid conclusion regarding the activity of the sympathoadrenal system can be drawn. Our study suggests that both increased cardiac output and reduced hepato-splanchnic blood flow (redistribution) contribute to the elevated blood flow previously demonstrated in various other organs and tissues in diabetic patients during poor metabolic control.     

A comparison of 4% succinylated gelatin solution versus normal saline in stable normovolaemic sheep: global haemodynamic, regional blood flow and oxygen delivery effects

The objective of this study was to compare the effects on regional blood flow and regional oxygen delivery of 4% succinylated gelatin solution (Gelofusine, B. Braun) with those of normal saline. This was a randomised, controlled, cross-over large animal study, which took place at the animal laboratory of university physiology institute. The subjects were seven merino cross-ewes. We implanted flow probes around the aorta, coronary, renal and mesenteric arteries. We randomised animals to observation (control), normal saline (one litre over 15 minutes) or Gelofusine (one litre over 15 minutes). We measured central haemodynamics, organ blood flows, arterial blood gases and haemoglobin every 30 minutes for 210 minutes. Compared to control, both Gelofusine and normal saline significantly and similarly increased mean arterial pressure, stroke volume, cardiac output and central venous pressure in the first hour (P < 0.05). Such changes, however, were transient except for the increase in cardiac output seen with Gelofusine. Normal saline significantly increased mesenteric blood flow in the first hour (P < 0.05), while Gelofusine caused a specific, sustained and progressive increase in renal blood flow and conductance (P < 0.05). Both fluids increased urine output and creatinine clearance (P < 0.05), but, due to haemodilution, both decreased renal oxygen delivery in the first hour (P < 0.05). Normal saline and Gelofusine have transient, volume expansion-related systemic haemodynamic effects, which are greater for Gelofusine. Saline had a more pronounced early effect on mesenteric blood flow, while Gelofusine had a sustained and progressive greater effect on renal blood flow. The transient increase in urine output and creatinine clearance seen with both fluids occurred while renal oxygen delivery decreased.     

Pulmonary blood flow distribution in lobar hypoxia--influence of cardiac output and nitric oxide inhalation.

Inhaled NO is reported to be less effective in patients with ARDS if cardiac output is high (> 10 L/min). It has also been demonstrated that increased blood flow and increased shear stress cause an enhancement of endogenous NO production. In one-lung ventilation and regional hypoxia, nitric oxide (NO) delivered to the ventilated lung may decrease blood flow to the nonventilated lung and improve arterial oxygenation. So far, however, results have been divergent. The present study was performed with the hypothesis that inhaled NO would be less effective if cardiac output was increased. In the anaesthetized pig, hypoxia (5% O2) was induced in the left lower lobe. NO was delivered consecutively to the hypoxic lobe and to the other, oxygenated parts, of the lungs during continuous measurement of lobar blood flow and total lung blood flow. Bleeding and infusion of dextran caused variation in cardiac output. It was found that lobar hypoxia per se reduced lobar blood flow from 22.9+/-3.1% to 4.7+/-0.9% of cardiac output. An increase (3.2+/-0.3 L x min(-1)) and a decrease (2.2+/-0.2 L x min(-1)) in cardiac output did not alter the relative perfusion of the hypoxic lobe from baseline cardiac output (2.6+/-0.2 L x min(-1)) values. When NO was delivered to the hypoxic lobe, there was a marked increase in relative lobar perfusion to 19.0+/-2.9% during low cardiac output and 16.5+/-2.7% during high cardiac output without any significant difference between the two NO-induced increases of lobar perfusion. The increase in lobar perfusion tended to depend inversely on total pulmonary blood flow when cardiac output had been reduced by bleeding but without reaching statistical significance (r = -0.42, p > 0.05). The decrease in mean pulmonary artery pressure and PaO2 seen during NO inhalation to the hypoxic lobe did not correlate with the level of cardiac output. When NO was delivered to the oxygenated parts of the lungs, no significant effect on relative lobar perfusion or arterial oxygenation was observed, either at raised or at lowered cardiac output. The findings give no further evidence to show that variations in cardiac output alter the effect of NO inhalation.     

Intestinal and hepatic perfusion and metabolism in hypodynamic endotoxic shock. Effects of nitric oxide synthase inhibition

Background: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects of a NOS-inhibitor on perfusion and metabolism during severe endotoxic shock.
Methods: Nineteen anaesthetised pigs were catheterised and ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of N^G-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with no further intervention.
Results: Endotoxin produced a hypodynamic shock with pulmonary hypertension. L-NAME did not increase arterial blood pressure, but deepened the fall in cardiac output and enhanced the increase in systemic and pulmonary vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. The addition of L-NAME induced a further decrease in the mesenteric artery flow only. L-NAME had no additional effect on hepatic artery flow ratio, while a transient decrease was seen in mesenteric flow ratio. Portal flow ratio decreased in the control group only. Global as well as regional oxygen extraction increased in both groups, more so in the L-NAME group. Lactate levels increased with no differences between the groups.
Conclusion: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.     

Systemic distribution of blood flow in swine while awake and during 1.0 and 1.5 MAC isoflurane anesthesia with or without 50% nitrous oxide

To examine the effects of isoflurane on systemic distribution of cardiac output, organ/tissue blood flow was measured in 11 isocapnic pigs using 15-micrometer diameter radionuclide-labeled microspheres injected into the left atrium. Measurements were made on each pig during five of the following six conditions; awake (control); 1.0 MAC (1.45% end-tidal)isoflurane anesthesia; 1.5 MAC (2.18% end-tidal) isoflurane anesthesia; 0.95% end-tidal isoflurane and 50% N2O anesthesia equivalent to 1.0 MAC; 1.68% end-tidal isoflurane and 50% N2O anesthesia equivalent to 1.5 MAC; and 50% N2O administration. The order of anesthetized steps was randomized. A period of 60 min was interposed between anesthetized steps to allow pigs to recover towards control values. Mean aortic pressure decreased in a dose-related manner during isoflurane anesthesia, whereas cardiac output decreased only during 1.5 MAC isoflurane anesthesia and heart rate remained unchanged. The addition of N2O attenuated the hypotensive effects of isoflurane and cardiac output was maintained near control values because of increased heart rate. Brain blood flow increased in a dose-dependent manner with isoflurane anesthesia, but myocardial blood flow exhibited a dose-related decrease. The addition of 50% N2O to maintain the same total MAC anesthesia resulted in a larger increase in brain blood flow especially at 1.5 MAC, while myocardial blood flow was maintained near control value. Rate-pressure product and myocardial blood flow at 1.5 MAC anesthesia were higher when N2O was used with isoflurane. While blood flow and fraction of cardiac output going to the adrenal glands were unaltered during isoflurane-N2O anesthesia, blood flow increased at 1.5 MAC isoflurane anesthesia. Splenic blood flow and splenic fraction of cardiac output were increased at both MAC levels of isoflurane as well as isoflurane-N2O anesthesia whereas blood flow to the stomach, small intestine, diaphragm, skeletal muscle, and adipose tissue decreased from control values. Renal, hepatic arterial, and cutaneous blood flow remained unaltered. Fifty percent N2O in the presence of a residual end-tidal isoflurane concentration of 0.20% caused heart rate to increase from control levels, while cardiac output and mean aortic pressure were unaltered. Brain blood flow increased by 27% above control values, but perfusion in the myocardium, adrenal glands, spleen, kidneys, liver, and skin was unchanged. Stomach, small intestine, skeletal muscle, and diaphragm blood flows decreased from control values, whereas perfusion of adipose tissue increased.     

Cardiac and Regional Hemodynamic Interactions between Halothane and Nitric Oxide Synthase Activity in Dogs

Background: In vitro, halothane appears to affect the role played by nitric oxide in the regulation of vascular tone and cardiac function. In vivo, the results of the interactions between halothane and the nitric oxide pathway remain controversial. The authors investigated the effects of halothane on the cardiac and regional hemodynamic properties of N-methyl-L-arginine (NMA), a specific nitric oxide synthase inhibitor, in dogs.

Methods: Twenty-five dogs were chronically instrumented. Aortic pressure, the first derivative of left ventricular pressure, cardiac output, heart rate, and carotid, coronary, mesenteric, hepatic, portal and renal blood flows were continuously recorded. N-methyl-L-arginine was infused intravenously at 20 mg/kg over 1 min in awake dogs (n = 11) and in 1.2% halothane-anesthetized dogs (n = 10). As a control group, the remaining four dogs were studied awake and during 1.2% halothane for 2 h in the absence of NMA.

Results: In awake dogs, NMA produced a sustained pressor response (34%) and systemic vasoconstriction (40%) associated with a decrease in cardiac output (16%). Regional circulation changes included an immediate and transient increase in carotid (43%) and coronary (237%) blood flows and a subsequent decrease in carotid blood flow (25%). Hepatic and mesenteric blood flows also decreased, by 43% and 16%, respectively. Except for the coronary circulation, regional vascular resistance increased significantly. Halothane did not affect the pressor response to NMA but did blunt the cardiac output changes. Consequently, the systemic vasoconstriction after nitric oxide synthase inhibition was of shorter duration and of lesser magnitude during halothane anesthesia. Halothane also blunted the carotid, mesenteric, and renal vasoconstriction induced by NMA. Finally, in 1.2% halothane-anesthetized dogs, NMA induced a coronary vasoconstriction.