Percentage Of Cardiac Output Research Articles

Age-dependent changes in cardiac output following balloon pulmonary angioplasty: Implications for combination therapy in chronic thromboembolic pulmonary hypertension

Abstract Background Balloon pulmonary angioplasty (BPA) is an accepted treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients still have exercise intolerance even after normalizing mean pulmonary arterial pressure with BPA. Although medical therapy may be a potential option for such patients, it cannot be necessary for all patients. Low cardiac output (CO) after BPA is associated with exercise intolerance. However, the change in CO with BPA could be affected by the patient’s age and pulmonary hypertension (PH) medication status. The specific patients’ characteristics that require medical therapy following BPA remain unknown. Methods This single-centre, retrospective observational study included 286 patients with CTEPH who underwent BPA and right heart catheterization one year BPA at our hospital. The patients were classified into three age groups (younger: age < 60 years, n=91; middle-aged: 60 ≤ age < 70 years, n=91; elderly: 70 years ≤ age, n=104), and also stratified by two groups based on PH medication status (Group 1: patients without PH medications before and after BPA, Group 2: patients who received PH medications before BPA and discontinued them after BPA). CO and its percent change were compared between Groups 1 and 2 in each age group. Results CO increased significantly in the younger group (4.3±0.2 to 4.5±0.1 L/min, p=0.040) and decreased in the elderly group (4.0±0.1 to 3.8±0.1 L/min, p=0.035), resulting in no significant change overall. CO in the younger and middle-aged groups significantly increased after BPA in Group 1, whereas in Group 2, those in the middle-aged and elderly groups significantly decreased after BPA. The percent CO changes declined in an age-dependent manner in both groups. Conclusions Increasing CO with BPA alone may be challenging in elderly patients. Adjuvant medical therapy might be necessary, even after successful BPA, especially in elderly patients.Percent change in CO stratified by age

Septic cardiomyopathy-diagnosis and estimation of disease severity

The relevance of septic cardiomyopathy is frequently underestimated due to the complexity of the pattern of cardiac injury and the corresponding difficulties in quantifying the degree of functional impairment. Account of the methods for diagnosis and severity classification of septic cardiomyopathy. Literature review and analysis of the main findings. Septic cardiomyopathy is characterized by both systolic and diastolic impairment of not only the left, but also the right ventricle, as well as by sinus-tachycardiomyopathy (≥ 90-95beats/min) of variable degree. Sepsis-related organ failure assessment (SOFA) score, left ventricular ejection fraction (LVEF), ECG and cardiac biomarkers do not help in grading severity of septic cardiomyopathy. For that purpose either asophisticated echocardiography diagnosis is mandatory, or the measurement of those global heart function parameters which take into account the dependency of cardiac output on afterload, in view of the pronounced vasodilatation in sepsis and septic shock, is needed. Asuitable parameter on the basis of cardiac output measurement is afterload-related cardiac performance (ACP), which gives the percentage of cardiac output in aseptic patient related to the cardiac output ahealthy heart pumps when challenged by afall in systemic vascular resistance to the same extent. The calculation of ACP shows that at least one in two septic patients suffers from impaired heart function and that mortality increases as severity increases. Simple parameters like LVEF are not apt for diagnosis nor for disease severity classification of septic cardiomyopathy. For that purpose either sophisticated echocardiography techniques or load-independent parameters-best validated-ACP measurements are appropriate.

A dumbbell rescue stent graft facilitates clamp-free repair of aortic injury in a porcine model

ObjectiveNoncompressible torso hemorrhage is a high-mortality injury. We previously reported improved outcomes with a retrievable rescue stent graft to temporize aortic hemorrhage in a porcine model while maintaining distal perfusion. A limitation was that the original cylindrical stent graft design prohibited simultaneous vascular repair, given the concern for suture ensnarement of the temporary stent. We hypothesized that a modified, dumbbell-shaped design would preserve distal perfusion and also offer a bloodless plane in the midsection, facilitating repair with the stent graft in place and improve the postrepair hemodynamics. MethodsIn an Institutional Animal Care and Use Committee-approved terminal porcine model, a custom retrievable dumbbell-shaped rescue stent graft (dRS) was fashioned from laser-cut nitinol and polytetrafluoroethylene covering and compared with aortic cross-clamping. Under anesthesia, the descending thoracic aorta was injured and then repaired with cross-clamping (n = 6) or dRS (n = 6). Angiography was performed in both groups. Operations were divided into phases: (1) baseline, (2) thoracic injury with either cross-clamp or dRS deployed, and (3) recovery, after which the clamp or dRS were removed. Target blood loss was 22% to simulate class II or III hemorrhagic shock. Shed blood was recovered with a Cell Saver and reinfused for resuscitation. Renal artery flow rates were recorded at baseline and during the repair phase and reported as a percentage of cardiac output. Phenylephrine pressor requirements were recorded. ResultsIn contrast with cross-clamped animals, dRS animals demonstrated both operative hemostasis and preserved flow beyond the dRS angiographically. Recovery phase mean arterial pressure, cardiac output, and right ventricular end-diastolic volume were significantly higher in dRS animals (P = .033, P = .015, and P = .012, respectively). Whereas distal femoral blood pressures were absent during cross-clamping, among the dRS animals, the carotid and femoral MAPs were not significantly different during the injury phase (P = .504). Cross-clamped animals demonstrated nearly absent renal artery flow, in contrast with dRS animals, which exhibited preserved perfusion (P<.0001). Femoral oxygen levels (partial pressure of oxygen) among a subset of animals further confirmed greater distal oxygenation during dRS deployment compared with cross-clamping (P = .006). After aortic repair and clamp or stent removal, cross-clamped animals demonstrated more significant hypotension, as demonstrated by increased pressor requirements over stented animals (P = .035). ConclusionsCompared with aortic cross-clamping, the dRS model demonstrated superior distal perfusion, while also facilitating simultaneous hemorrhage control and aortic repair. This study demonstrates a promising alternative to aortic cross-clamping to decrease distal ischemia and avoid the unfavorable hemodynamics that accompany clamp reperfusion. Future studies will assess differences in ischemic injury and physiological outcomes. Clinical RelevanceNoncompressible aortic hemorrhage remains a high-mortality injury, and current damage control options are limited by ischemic complications. We have previously reported a retrievable stent graft to allow rapid hemorrhage control, preserved distal perfusion, and removal at the primary repair. The prior cylindrical stent graft was limited by the inability to suture the aorta over the stent graft owing to risk of ensnarement. This large animal study explored a dumbbell retrievable stent with a bloodless plane to allow suture placement with the stent in place. This approach improved distal perfusion and hemodynamics over clamp repair and heralds the potential for aortic repair while avoiding complications.

(625) - Veno-arterial Shunting Is Tolerated in a Canine Model of Partial Ventricular Assist

The etiology of worsening renal function in chronic heart failure is incompletely understood. Chronic left ventricular failure, the resulting right ventricular fluid overload and elevated central venous pressure (CVP) have been implicated in deteriorating renal function. We hypothesized that shunting of right sided blood into the arterial system by using a peripherally inserted centrifugal pump (active shunting) would decrease right sided pressures, augment afterload and improve renal function. The amount of blood as percent of cardiac output that can be shunted without significant systemic desaturation was investigated in this study.

Optimum positive end-expiratory pressure 40 years later.

In 1975, Suter and colleagues published a fascinating study trying to determine the “optimum” level of end-expiratory pressure (PEEP) in patients with acute respiratory failure receiving mechanical ventilation.[1] The fascinating aspect of the paper was that they proposed a physiological model of the acute respiratory distress syndrome (ARDS) based on the relationship between lung volume, respiratory mechanics (compliance), dead space, cardiac output, and shunt and oxygenation. This model is still very useful today. Some of the messages of this paper should not be forgotten: Although increasing PEEP seemed to be beneficial, it had a double effect and above a certain value, PEEP was probably more risky than beneficial, with increase in dead space and reduction in cardiac output and oxygen delivery. The message about oxygen delivery was important, stressing that what really mattered was not the level of PaO2 in the blood but the quantity of oxygen carried by hemoglobin, as measured by oxygen transport. Therefore, increasing PaO2 at the expense of a decrease in cardiac output would result in a net negative effect in terms of oxygen delivered to the tissue. If the goal of PEEP is to increase oxygenation, this makes a lot of sense and continuing to look at PaO2 without considering cardiac output is conceptually a major limitation.[2] In addition, a positive relationship between shunt, i.e. the percentage of cardiac output passing through non-ventilated areas, and cardiac output was demonstrated.[3] Dantzker, a few years later, even suggested that an important reason for the observed improvement in oxygenation with PEEP in ARDS was the reduction in cardiac output and the shunt-cardiac output relationship.[4] It was also demonstrated later, however, that maintaining cardiac output with inotropic agents had significant benefits of PEEP on oxygenation.[5]

Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin Resistance

Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet–induced muscle insulin resistance were tested. We show that muscle HA was increased in HF diet–induced obese (DIO) mice and that treatment of PEGPH20, which dose-dependently reduced HA in muscle ECM, decreased fat mass, adipocyte size, and hepatic and muscle insulin resistance in DIO mice at 10 mg/kg. Reduced muscle insulin resistance was associated with increased insulin signaling, muscle vascularization, and percent cardiac output to muscle rather than insulin sensitization of muscle per se. Dose-response studies revealed that PEGPH20 dose-dependently increased insulin sensitivity in DIO mice with a minimally effective dose of 0.01 mg/kg. PEGPH20 at doses of 0.1 and 1 mg/kg reduced muscle HA to levels seen in chow-fed mice, decreased fat mass, and increased muscle glucose uptake. These findings suggest that ECM HA is a target for treatment of insulin resistance.

Alpha-adrenergic contribution to the cardiovascular response to acute hypoxemia in the chick embryo.

Fetal responses to acute hypoxemia include bradycardia, increase in blood pressure, and peripheral vasoconstriction. Peripheral vasoconstriction contributes to the redistribution of the cardiac output away from ancillary vascular beds toward myocardial, cerebral, and adrenal circulations. We investigated the effect of alpha-adrenergic receptor blockade on this fetal response. Fluorescent microspheres were used to measure cardiac output distribution during basal and hypoxemic conditions with and without phentolamine treatment. Phentolamine altered basal cardiac output distribution, indicating a basal alpha-adrenergic tone, but this was mainly noted at the earlier stages of incubation. During hypoxemia, phentolamine prevented vasoconstriction in the carcass. At day 19 of incubation, the percent cardiac output distributed to the carcass increased by 20% compared with a decrease in the control group by 17%. Phentolamine markedly attenuated the subsequent redistribution of the cardiac output toward the brain (from +102% in the control group to -25% in the phentolamine-treated group) and the heart (from +196% in the control group to +69% in the phentolamine-treated group). In the chick embryo, alpha-adrenergic mechanisms contribute to the maintenance of basal vascular tone and to the redistribution of the cardiac output away from the peripheral circulations toward the brain and heart during hypoxemic conditions.

Blood flow distribution and tissue allometry in channel catfish

Blood flow (as percentage of cardiac output) in fasted channel catfish acclimated to 21°C was directed primarily to white muscle (72%) followed by head kidney (5·7%), red muscle (5·5%), trunk kidney (3·1%), liver (2·2%), swim bladder (1·4%) and skin (1·1%). The stomach, intestines, pyloric caeca, gonads, brain, abdominal fat and spleen contained &lt;0·5% of blood flow. There was considerable interfish variation among blood flow distribution to visceral organs with substantial spatial heterogeneity of blood flow to white muscle. The spatial heterogeneity of flow to muscle prevented accurate estimation of total flow to this tissue based on the microsphere deposition of a few sub‐samples. Instead, a novel approach, based on the whole animal counting of the eviscerated carcass was used to measure blood flow to white muscle. The scaling relationships for tissue mass in catfish (63–1873 g) followed the allometric equation (aWb) and tended to exhibit negative allometry, with organ weight decreasing in proportion to body weight. The b values for most tissues ranged between 0·83 and 1·0. The relative mass of the brain showed the greatest decline and with a b value of 0·32. The results, together with previous data on cardiac output, permitted calculation of organ blood flow rates in channel catfish. © 1999 The Fisheries Society of the British Isles

Effects of aging on cardiac output, regional blood flow, and body composition in Fischer-344 rats.

The purpose of this study was to determine the effects of maturation and aging on cardiac output, the distribution of cardiac output, tissue blood flow (determined by using the radioactive-microsphere technique), and body composition in conscious juvenile (2-mo-old), adult (6-mo-old), and aged (24-mo-old) male Fischer-344 rats. Cardiac output was lower in juvenile rats (51 +/- 4 ml/min) than in adult (106 +/- 5 ml/min) or aged (119 +/- 10 ml/min) rats, but cardiac index was not different among groups. The proportion of cardiac output going to most tissues did not change with increasing age. However, the fraction of cardiac output to brain and spinal cord tissue and to skeletal muscle was greater in juvenile rats than that in the two adult groups. In addition, aged rats had a greater percent cardiac output to adipose tissue and a lower percent cardiac output to cutaneous and reproductive tissues than that in juvenile and adult rats. Differences in age also had little effect on mass-specific perfusion rates in most tissues. However, juvenile rats had lower flows to the pancreas, gastrointestinal tract, thyroid and parathyroid glands, and kidneys than did adult rats, and aged rats had lower flows to the white portion of rectus femoris muscle, spleen, thyroid and parathyroid glands, and prostate gland than did adult rats. Body mass of juvenile rats was composed of a lower percent adipose mass and a greater fraction of brain and spinal cord, heart, kidney, liver, and skeletal muscle than that of the adult and aged animals. Relative to the young adult rats, the body mass of aged animals had a greater percent adipose tissue mass and a lower percent skeletal muscle and skin mass. These data demonstrate that maturation and aging have a significant effect on the distribution of cardiac output but relatively little influence on mass-specific tissue perfusion rates in conscious rats. The old-age-related alterations in cardiac output distribution to adipose and cutaneous tissues appear to be associated with the increases in percent body fat and the decreases in the fraction of skin mass, respectively, whereas the decrease in the portion of cardiac output directed to reproductive tissue of aged rats appears to be related to a decrease in mass-specific blood flow to the prostate gland.

The Effect of Dopexamine on Ventilation Perfusion Distribution and Pulmonary Gas Exchange in Anesthetized, Paralyzed Patients

We studied the effects of the beta2-adrenoceptor and DA1-receptor agonist dopexamine on ventilation perfusion (V(A)/Q) distribution in anesthetized, paralyzed patients (n = 17) undergoing major abdominal surgery. Intrapulmonary shunt (Q(S)/Q(T)) (percentage of cardiac output [CO]), perfusion of low V(A)/Q areas (percentage of CO), ventilation of high V(A)/Q areas (percentage of total ventilation [V(E)]), and dead space ventilation [percentage of V(E)]) were calculated from the retention/excretion data of six inert gases. In the control state, Q(S)/Q(T) was 11% +/- 9% (mean +/- SD) and little perfusion of low V(A)/Q areas (3% +/- 4%) was observed. Infusion of 1.0 microg kg(-1) x min(-1) dopexamine had no effect on Q(S)/Q(T) and low V(A)/Q areas despite an increased CO (7.7 +/- 2.2 L/min versus 6.2 +/- 1.2 L/min; P < 0.01). Pao2 increased from 15.5 +/- 5.6 kPa (116 +/- 42 mm Hg) to 17.3 +/- 6.3 kPa (130 +/- 47 mm Hg) (P < 0.05). Infusion of 2.0 microg x kg(-1) x min(-1) dopexamine further increased CO to 8.4 +/- 2.7 L/min (P < 0.01) without alterations of Q(S)/Q(T), perfusion of low V(A)/Q areas, and Pao2. We concluded that dopexamine (1.0 microg x kg(-1) x min(-1) and 2.0 microg x kg(-1) x min(-1)) has no adverse effects on V(A)/Q relationships and Q(S)/Q(T) in anesthetized, paralyzed patients.The I.V. administration of vasoactive drugs can improve oxygen delivery to different organ systems but may impair pulmonary gas exchange. In anesthetized, paralyzed patients, we studied the effects of beta2-adrenoceptor and DA1-receptor agonist dopexamine on ventilation perfusion distribution. Dopexamine (1.0 microg x kg(-1) x min(-1) and 2.0 microg x kg(-1) min(-1)) improved cardiac output and oxygenation without alterations of intrapulmonary shunt.

The effect of dopexamine on ventilation perfusion distribution and pulmonary gas exchange in anesthetized, paralyzed patients.

We studied the effects of the beta2-adrenoceptor and DA1-receptor agonist dopexamine on ventilation perfusion (V(A)/Q) distribution in anesthetized, paralyzed patients (n = 17) undergoing major abdominal surgery. Intrapulmonary shunt (Q(S)/Q(T)) (percentage of cardiac output [CO]), perfusion of low V(A)/Q areas (percentage of CO), ventilation of high V(A)/Q areas (percentage of total ventilation [V(E)]), and dead space ventilation [percentage of V(E)]) were calculated from the retention/excretion data of six inert gases. In the control state, Q(S)/Q(T) was 11% +/- 9% (mean +/- SD) and little perfusion of low V(A)/Q areas (3% +/- 4%) was observed. Infusion of 1.0 microg kg(-1) x min(-1) dopexamine had no effect on Q(S)/Q(T) and low V(A)/Q areas despite an increased CO (7.7 +/- 2.2 L/min versus 6.2 +/- 1.2 L/min; P < 0.01). Pao2 increased from 15.5 +/- 5.6 kPa (116 +/- 42 mm Hg) to 17.3 +/- 6.3 kPa (130 +/- 47 mm Hg) (P < 0.05). Infusion of 2.0 microg x kg(-1) x min(-1) dopexamine further increased CO to 8.4 +/- 2.7 L/min (P < 0.01) without alterations of Q(S)/Q(T), perfusion of low V(A)/Q areas, and Pao2. We concluded that dopexamine (1.0 microg x kg(-1) x min(-1) and 2.0 microg x kg(-1) x min(-1)) has no adverse effects on V(A)/Q relationships and Q(S)/Q(T) in anesthetized, paralyzed patients. The I.V. administration of vasoactive drugs can improve oxygen delivery to different organ systems but may impair pulmonary gas exchange. In anesthetized, paralyzed patients, we studied the effects of beta2-adrenoceptor and DA1-receptor agonist dopexamine on ventilation perfusion distribution. Dopexamine (1.0 microg x kg(-1) x min(-1) and 2.0 microg x kg(-1) min(-1)) improved cardiac output and oxygenation without alterations of intrapulmonary shunt.

Hepatic haemodynamics and reticuloendothelial function in the rat in response to chronic ethanol administration

This study investigated the effects of chronic ethanol intake on hepatic haemodynamics and reticuloendothelial system function in the rat. Comparisons were also made with blood flow to pancreas, kidney, spleen, lung and skin. Male Wistar rats, approximately 0.15 kg initial body weight, were fed a diet containing 35% of the total calories as ethanol. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. The hepatic perfusion index and reticuloendothelial function was determined with [(99m) Tc]-labelled sulphur colloid [(99m) Tc]-SC) and blood flow with radiolabelled microspheres under anaesthesia. After 4-5 weeks the weights of liver and skin of alcohol fed rats decreased by 10% (p= 0.040) and 23% (p= 0.024), respectively, compared to controls and there was a small increase in kidney weight (15%, p = 0.001). Blood flow to liver, pancreas, kidney, spleen, lung and skin was not altered significantly by chronic alcohol administration, irrespective of whether the data were expressed as a percentage of cardiac output, blood flow per minute per organ or blood flow per minute per g tissue weight (p > 0.113 in all instances). However, there was a significant increase in splenic reticuloendothelial system activity (+ 121%, p = 0.018). Hepatic reticuloendothelial system activity was also increased (+ 22%, p = 0.061). Chronic alcohol administration resulted in significant increases in portal pressure (+ 55%, p = 0.042) and portal venous resistance (+ 66%, p = 0.001), but portal venous inflow and hepatic perfusion index were not altered compared to controls The results of this study indicated that chronic alcohol administration did not alter visceral blood flow significantly, but did increase portal pressure, portal vascular resistance and reticuloendothelial system activity.

A new in vivo method for the direct measurement of nutrient artery blood flow.

A new method of directly measuring nutrient artery blood flow using ultrasonic probes is described. These probes have provided reproducible results in our experiments. Advantages of ultrasonic probes include the direct measurement of blood flow through small arteries, ease of use, accuracy of measurement, applicability to a wide range of vessel diameters, the capability of chronically monitoring blood flow over time using permanently implanted probes, and the ability to use the method in conjunction with previous methods of bone blood flow measurement. The method is limited to the extent that only the contribution of the nutrient artery can be measured and total bone blood flow cannot be assessed. Tibial nutrient arterial flow and cardiac output were measured in adult mongrel dogs. Two experiments were performed: 1) bilateral baseline tibial nutrient artery blood flow measurements over time and 2) tibial nutrient blood flow comparing inhaled anesthesia (halothane/nitrous oxide/oxygen) and intravenous anesthesia (pentobarbital [Nembutal]). In 15 mongrel dogs, tibial nutrient artery blood flow averaged 1.46 +/- 0.72 mL/min (0.09 +/- 0.05 percent of cardiac output and 2.75 +/- 1.95 mL/min/100 g of bone). No significant difference in tibial nutrient artery blood flow was observed between animals given intravenous and inhaled anesthesia (P > .05). As a basic research tool, transit-time ultrasonic blood flow technology may be useful. The method is relatively easy to use and may be applied to experimental models designed to investigate various physiologic and pathologic states frequently encountered in orthopedics (eg, shock, sepsis, fractures).

Renal hemodynamics in rats with myocardial infarction: selective antagonism of angiotensin receptor subtypes.

Rats with congestive heart failure demonstrate striking intrarenal vasoconstriction that contributes to reduced renal excretory function. The importance of specific angiotensin II receptor subtypes (AT1, AT2) for mediating changes in renal hemodynamics was studied in anesthetized rats 1 mo after myocardial infarction (MI) created by coronary artery ligation. AT1 antagonism with losartan alone decreased mean arterial pressure (MAP), total peripheral resistance (TPR), and renal resistance (RR) in control and MI rats to a similar extent without affecting renal blood flow (RBF) or RBF as a percentage of cardiac output (%RBF/CO). In contrast, AT2 antagonism with PD-123319 alone significantly reduced MAP and RR in MI rats without affecting these parameters in control rats. TPR and %RBF/CO were not changed significantly in either group. In contrast, combined AT1- and AT2-receptor inhibition lowered TPR and RR and increased RBF and %RBF/CO, thus the effects of renin or ACE inhibition were mimicked in MI rats. We conclude that angiotensin II acts at both AT1 and AT2 receptor sites in rats with reduced cardiac mass to modulate renal hemodynamics.

Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hypercapnia

To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia. Prospective, controlled study. Research laboratory. Female Marino ewes. Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n = 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n = 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation). Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 +/- 0.03 at normocapnia to 7.14 +/- 0.01 (p < .01 vs. normocapnia) as blood PCO2 increased to 81.2 +/- 1.8 torr (10.8 +/- 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 +/- 0.02 at normocapnia and was maintained at 7.37 +/- 0.01 while PaCO2 was increased to 80.3 +/- 0.9 torr (10.7 +/- 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 +/- 0.6 L/min at normocapnia vs. 6.8 +/- 1.0 L/min at 1 hr [p < .05]; pH-corrected group: 4.1 +/- 0.4 at normocapnia vs. 5.7 +/- 0.4 L/min at 1 hr [p < .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p < .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p < .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 +/- 1.5 mm Hg at normocapnia vs. 26.8 +/- 5.1 at 1 hr, p < .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 +/- 1.6 mm Hg at normocapnia to 7.7 +/- 4.2 at 1 hr). Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.

Predictable reduction in left ventricular stroke work and oxygen utilization with an implantable centrifugal pump

Previous investigations with roller pumps and pneumatic pulsatile assist devices have demonstrated that nearly complete capture of normal left ventricular end-diastolic volume was necessary for appreciable reductions in oxygen consumption and stroke work. We tested the hypothesis that a centrifugal pump would decrease left ventricular stroke work and oxygen consumption as a function of pump flow. Ten sheep (35 to 50 kg) were instrumented and placed on left atrium-to-descending aorta bypass with a small, lightweight (112 g), implantable centrifugal pump. The relations between pump flow as a percent of cardiac output (% bypass), left ventricular stroke work, and oxygen consumption were studied. Left ventricular stroke work was calculated from the pressure-volume loops obtained with micromanometer and conductance catheters and was indexed per 100 g of left ventricular wet weight. Oxygen consumption was calculated from left main coronary artery blood flow and the arterial-coronary sinus oxygen content difference, normalized to 100 g of left ventricular wet weight and a heart rate of 100 beats/min. Measurements were made in stepwise increments of pump flow from zero to the maximum obtainable and then reversed in similar decrements. Analyses were made for 27 complete runs. Our data demonstrate that reductions in left ventricular stroke work and oxygen consumption were achieved from zero to maximal bypass. There was an approximate 66% and 50% reduction in left ventricular stroke work and oxygen consumption, respectively, at 60% bypass. Thus, in contrast to other types of assist devices, our centrifugal pump in a left atrium-to-aorta circuit provides predictable and significant reductions in left ventricular stroke work and oxygen consumption at moderate levels of bypass. These data establish the physiogic bases for use of this device as temporary assist in patients with postcardiotomy low flow states.

Application andIn situcalibration of a pulsed-doppler flowmeter for blood flow measurement in crustaceans

The pulsed-Doppler flowmeter permits continuous, non-invasive measurement of blood flow through several arteries simultaneously. Summation of volume flow rates through all arteries leaving the heart allows determination of cardiac output, stroke volume, and the percentage of cardiac output delivered to each region of the body. The use of this system for investigating changes in arterial perfusion as well as its calibrationin situare described.

Regional circulatory and systemic hemodynamic effects of diaspirin cross-linked hemoglobin in the rat.

Diaspirin cross-linked hemoglobin (DCLHb) (Baxter Healthcare Corporation) is a promising resuscitative fluid. The effect of DCLHb (400 mg/kg, i.v.), on regional circulation and systemic hemodynamics was studied in male Sprague-Dawley rats using a radioactive microsphere technique. Systemic hemodynamics, distribution of cardiac output, regional blood flow and vascular resistance were determined before (baseline) and 15, 30 and 60 min after the administration of DCLHb. Infusion of an equal volume of saline did not produce any significant change in systemic hemodynamics or regional circulation. DCLHb produced an increase (79%) in the mean blood pressure which lasted for more than 60 min. Heart rate, cardiac output and stroke volume were not significantly affected, while total peripheral resistance was increased after the administration of DCLHb. DCLHb produced significant increases in blood flow to the heart, gastrointestinal tract (GIT), portal system and skin. The blood flow to the kidney, brain and musculoskeletal system was not significantly affected by DCLHb. The vascular resistance was not altered in the heart, brain, GIT, portal system, kidney or skin, but there was a marked increase in the vascular resistance in the musculoskeletal system. There was a significant increase in the percentage of cardiac output to visceral organs like heart, GIT and portal system, while a marked decrease in the percent cardiac output to musculoskeletal system was observed with DCLHb. It is concluded that the blood flow to most of the organs is either increased or is not affected by DCLHb.

Effect of stroma-free hemoglobin and diaspirin cross-linked hemoglogbin on the regional circulation and systematic hemodynamics

The effects of unmodified stroma-free hemoglobin (SFHb) and diaspirin cross-linked hemoglobin (DCLHb) on the regional blood circulation and systematic hemodynamics were studied in rats using a radioactive microsphere technique. SFHb and DCLHb increased mean arterial blood pressure without affecting heart rate. SFHb produced a 24.9 % decrease in the cardiac output while DCLHb produced an 44.8 % increase in the cardiac output. Stroke volume was decreased (−27.3 %) by SFHb and increased (+36.4 %) by DCLHb. Total peripheral resistance increased with both SFHb and DCLHb. DCLHb increased blood flow to the heart, spleen, stomach, small intestine and skin, and had no effect on blood flow to the brain, kidneys, liver, mesentery, pancreas, caecum, large intestine and musculo-skeletal system. In contrast, in animals infused with SFHb, blood flow decreased to the kidneys, liver and spleen, increased to the heart, small intestine and skin, and had no effect to the brain, caecum, large intestine and musculo-skeletal system. DCLHb had no effect on vascular resistance in any organ except for an increase in the musculo-skeletal system. In contrast, SFHb increased vascular resistance in the kidneys, liver, spleen, skin, mesentery and pancreas, and had no effect on vascular resistance in the musculo-skeletal system, brain, heart, stomach, small intestine, caecum and large intestine. SFHb had no effect on distribution of cardiac output to the brain, gastrointestinal tract (GIT), kidneys, skin, musculo-skeletal and portal system, while DCLHb significantly decreased the percent cardiac output to the musculo-skeletal system. DCLHb did not affect the distribution of cardiac output to the brain, GIT, kidneys, skin and portal system. SFHb and DCLHb increased the percent cardiac output to the heart. It is concluded that similar concentrations and doses of DCLHb and SFHb produce different effects on the regional blood circulation and systematic hemodynamics.

Effects of administration of basic fibroblast growth factor on hypoxic fractions in xenografted DLD-2 human tumours: time dependence

A previous publication (Leith et al., 1992) showed that administration of basic fibroblast growth factor (FGF-2, 0.25 mg kg-1, q.i.d. x 7) to mice bearing xenografted DLD-2 human colon cancers would increase treated tumour growth rates as compared to control neoplasms. Additionally, at the end of the 7 day treatment period, clonogenic excision assays showed that the percentage of hypoxic cells in tumours from mice receiving FGF-2 administration was significantly decreased as compared to control neoplasms (from about 42 to about 19%). The present study was undertaken to better define the kinetics of changes in hypoxic percentages as a function of tumour volume and FGF-2 treatment. In sham-injected control tumours, the hypoxic percentage increased from about 14% at day 15 postimplantation, (i.e. when sham- or FGF-2 injections were begun) to about 42% by day 22, and to about 75% at 29 days postimplantation (respective average volumes 220, 910, and 2810 mm3). In contrast, the hypoxic percentages in mice treated with FGF-2 remained at the levels seen in control mice on day 15, not only throughout the 7 day FGF-2 treatment schedule, but for at least 1 week after the cessation of growth factor administration. The hypoxic percentage was 16% on day 29 postimplantation, even though average tumour volumes were about 4325 mm3. These data show that the effect of FGF-2 administration on tumour growth rate and hypoxic percentages in xenografted DLD-2 neoplasms is rapid, and continues for some period of time even after administration is ended. Studies of tumour perfusion with injected 86RbCl at equivalent tumour volumes of about 1800 mm3 indicated that the percentage of cardiac output to FGF-2 treated tumours was 33% greater than in sham-injected control neoplasms.