Biomedical subjects

K R Walley

Publications and source records attributed to K R Walley.

At least 55 records · Page 3Linked to original sources

PubMed1996

Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia.

Decreased contractility of myocytes after cytokine exposure can be prevented by nitric oxide synthase inhibition. Whether this is true in an intact animal model of sepsis is unknown. Anesthetized pigs were pretreated with saline or a nitric oxide synthase inhibitor, N omega-nitro-L-arginine, and then treated with saline or endotoxin. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (E(max)) of the end-systolic pressure-volume relationship. Four hours after endotoxin infusion, E(max) had decreased by 44 +/- 5% (P < 0.05) and mean arterial pressure had decreased by 30 +/- 10% (P < 0.05). Pretreatment with N omega-nitro-L-arginine significantly reduced the decrease in E(max) to 28 +/- 3% (P < 0.05) and prevented the decrease in mean arterial pressure. However, it also raised pulmonary arterial pressure. We conclude that nitric oxide contributes to the early decrease in left ventricular contractility after endotoxin in the intact animal. However, the vascular effects of nitric oxide synthase inhibition increase right and left ventricular afterloads, which were detrimental to cardiac function.

Animals↗

PubMed1996

Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory.

The hypothesis that the distribution of oxygen demand in relation to oxygen supply (dO2/qO2) effects oxygen extraction in peripheral tissues was tested. By using a simple theoretical model, realistic biphasic oxygen consumption-delivery relationships were predicted from dO2/qO2 distributions. Increasing width (relative dispersion) of the dO2/qO2 distribution, indicating mismatch between oxygen demand and supply, nonlinearly decreased the critical oxygen extraction ratio (calculated by using dual-line regression). Skewed dO2/qO2 distributions had a lesser effect. Incomplete oxygen uptake, due to diffusion limitation or other causes of physiological arteriovenous shunt, linearly decreased the critical oxygen extraction ratio. Approximate dO2/qO2 distributions were then estimated from previously reported capillary transit-time distributions. Critical oxygen extraction ratios predicted from these estimated dO2/qO2 distributions match reported values. This theoretical approach also predicts the decrease in the critical oxygen extraction ratio in porcine gut after endotoxin infusion in the companion paper (M. F. Humer, P. T. Phang, B. P. Friesen, M. F. Allard, C. M. Goddard, and K. R. Walley. J. Appl. Physiol. 81: 895-904, 1996). Much as pulmonary ventilation-perfusion relationships account for pulmonary gas exchange, dO2/qO2 distributions quantitatively account for measured tissue oxygen extraction and predict novel features of the relationship between heterogeneity and oxygen extraction.

Animals↗

PubMed1996

Heterogeneity of gut capillary transit times and impaired gut oxygen extraction in endotoxemic pigs.

We tested the hypothesis that endotoxin increases the heterogeneity of gut capillary transit times and impairs oxygen extraction. The gut critical oxygen extraction ratio was determined by measuring multiple oxygen delivery-consumption points during progressive phlebotomy in eight control and eight endotoxin-infused anesthetized pigs. In multiple 1- to 2-g samples of small bowel, we measured blood volume (radiolabeled red blood cells) and flow (radiolabeled 15-microns microspheres) before and after critical oxygen extraction. Red blood cell transit time (= volume/flow) multiplied by morphologically determined capillary/total blood volume gave capillary transit time. During hemorrhage, capillary/total blood volume did not change in the endotoxin group (0.5 +/- 4.5%) but increased in the control group (17.6 +/- 2.5%; P < 0.05) due to a decrease in total gut blood volume. Flow decreased significantly in the endotoxin group (36 +/- 10%; P < 0.05) but not in the control group (12 +/- 10%). Capillary transit-time heterogeneity increased in the endotoxin group (12.3 +/- 4.9%) compared with the control group (-5.8 +/- 7.4%; P < 0.05), predicting a critical oxygen extraction ratio 0.14 lower in the endotoxin group than in the control group (K. R. Walley. J. Appl. Physiol. 81: 885-894, 1996). This matches the measured difference (endotoxin group, 0.60 +/- 0.04; control group, 0.74 +/- 0.03; P < 0.05). Increased heterogeneity of capillary transit times may be an important cause of impaired oxygen extraction.

Animals↗

PubMed1995

Different effects of histamine H1 and H2 stimulation on left ventricular contractility in pigs.

Histamine decreases ventricular contractility in some settings but increases it in others. To better understand these apparently discrepant results, we measured hemodynamics and left ventricular pressure (Millar catheter) and volume (ultrasonic crystals) in atrially paced, alpha- and beta-antagonist-treated pigs. Histamine was infused (0.5-10 micrograms.kg-1.min-1) before and after H2-antagonist (ranitidine) pretreatment. Changes in left ventricular contractile function were measured as shift of the end-systolic pressure-volume relationship (delta ESPVR) at a pressure of 100 mmHg. We found that at low doses (0.5 and 1 micrograms.kg-1.min-1), histamine significantly decreased delta ESPVR (-1.1 +/- 1.4 ml, P < 0.05) after H2-antagonist pretreatment. At doses above 1 micrograms.kg-1.min-1, histamine increased contractility in a dose-response fashion [maximum effect: 5.1 +/- 3.3 ml, dose resulting in 50% effect (ED50): 0.75 +/- 1.79 micrograms.kg-1.min-1] that was best described using a Hill coefficient of 2. Ranitidine increased the ED50 by approximately one order of magnitude (0.75 +/- 1.79 to 9.50 +/- 2.60 micrograms.kg-1.min-1, P < 0.05). We conclude that in vivo, at higher doses, histamine increases left ventricular contractility via H2-receptor stimulation, whereas at low doses histamine decreases left ventricular contractility, probably via H1-receptor stimulation.

Animals↗

PubMed1995

Prolonged leukocyte transit time in coronary microcirculation of endotoxemic pigs.

We quantified the timing and extent of leukocyte retention by the coronary microcirculation in a pig model of hyperdynamic sepsis in three ways. First, the transmyocardial leukocyte gradient was determined as coronary blood flow (calibrated ultrasonic flow probe) multiplied by the difference between leukocyte counts in the aorta and coronary sinus. Measurements were taken at 1-min intervals for 30 min and then at 3-min intervals for 45 min in anesthetized pigs exposed to either endotoxin (50 micrograms/kg iv over 30 min) (n = 7) or vehicle (n = 7). Second, postmortem morphometric analysis was used to quantitate the number and location of retained myocardial leukocytes. Finally, myocardial capillary transit time of leukocytes was calculated from the above measures. In the endotoxin group 2.1 +/- 0.8 x 10(9) leukocytes/100 g wet wt were retained in the coronary circulation, primarily in capillaries. This resulted in 111 +/- 37 (P < 0.05) times as many leukocytes in the coronary microcirculation than predicted from the arterial leukocyte concentration. Myocardial capillary transit time of leukocytes was prolonged to 39.1 +/- 20.6 s (P < 0.05) in the endotoxin group versus 5.0 +/- 1.4 s in the control group. We conclude that, after endotoxin infusion in a pig model of hyperdynamic sepsis, myocardial leukocyte transit is slowed, leading to the retention of large numbers of leukocytes in the coronary microcirculation.

Animals↗

PubMed1995

Myocardial oxygen extraction ratio is decreased during endotoxemia in pigs.

Why the myocardial oxygen extraction ratio (ERm) is decreased during septic shock in humans is unknown. Therefore, we calculated ERm in 15 anesthetized pigs by measuring arterial and coronary venous oxygen content. We measured myocardial lactate flux, myocardial contractility, and global myocardial blood flow and its distribution. After baseline measurements, animals received either saline (n = 6) or 50 micrograms/kg of endotoxin (n = 9). Measurements were repeated for 4 h. After endotoxin, ERm decreased from 67 +/- 12% at baseline to 36 +/- 10% (P < 0.01) at 1 h and 54 +/- 10% (P < 0.05) at 4 h, associated with an increased myocardial blood flow that was heterogeneous. Neither myocardial oxygen nor lactate consumption decreased in the endotoxin group, and changes in left ventricular contractility were not correlated with changes in ERm. We conclude that the decrease in ERm after endotoxin infusion is due to both increased blood flow and mismatching between myocardial oxygen delivery and demand. Impaired myocardial oxygen extraction capacity during sepsis did not cause global myocardial tissue hypoxia.

Animals↗

PubMed1995

Anti-tumor necrosis factor-alpha prevents decreased ventricular contractility in endotoxemic pigs.

It is not known how the decrease in left ventricular contractility following endotoxin exposure is mediated, or whether this decrease is preventable by antibodies to tumor necrosis factor-alpha (TNF alpha). Four groups of six anesthetized and instrumented pigs were pretreated with ovine polyclonal antibody to human TNF alpha (anti-TNF alpha), nonspecific IgG, or saline, and then treated with either endotoxin or saline. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (Emax) of the end-systolic pressure-volume relationship. Four hours after the start of endotoxin infusion in the nonspecific IgG pretreated group, Emax had decreased by 44 +/- 6% (p < 0.05), mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p < 0.05), and cardiac output was rapidly decreasing after an initial increase (p < 0.05). Anti-TNF alpha significantly reduced the decrease in Emax (11 +/- 9%, p < 0.05), and the systemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p < 0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests that TNF alpha is an important early mediator in sepsis leading to decreased left ventricular contractility.

Animals↗

PubMed1995

Amrinone increases ventricular contractility and diastolic compliance in endotoxemia.

Systolic and diastolic dysfunction occur during human septic shock, and sensitivity to beta-adrenergic agents is reduced. We sought to determine whether amrinone, an inotropic agent independent of beta-receptors, increases left-ventricular contractility or diastolic compliance after endotoxin infusion. We measured left-ventricular volume (using a conductance catheter) and pressure (using a Millar catheter) before and after administering amrinone (4.5 mg/kg i.v., then 10 micrograms/kg/min) to six endotoxemic and seven control pigs. The slope of the end-systolic pressure-volume relationship, Ees, was used as the primary measure of contractility. Diastolic stiffness was characterized using stiffness parameters taken from pressure-volume relationships (k) and from pressure-volume strain relationships. Amrinone increased Ees from a median of 10.4 mm Hg/ml (interquartile range, 7.2 to 12.3) to 16.4 (13.7 to 18.6) (p < 0.05) in the endotoxin group (p < 0.05). Amrinone decreased diastolic stiffness (k) in the endotoxin group by 35 +/- 18% (p < 0.05). Amrinone did not significantly change Ees or k in the control group. Mean arterial pressure decreased after endotoxin infusion from 117 +/- 23 mm Hg to 76.5 +/- 14.9 mm Hg (p < 0.05), and decreased further after amrinone to 62.0 +/- 14.8 mm Hg (p < 0.05). We conclude that in this model of sepsis, amrinone may beneficially increase systolic contractility and diastolic compliance, but may dangerously decrease an already low mean arterial pressure.

Amrinone↗

PubMed1994

Carbon dioxide absorption is not linearly related to intraperitoneal carbon dioxide insufflation pressure in pigs.

BACKGROUND: Carbon dioxide absorption into the blood during laparoscopic surgery using intraperitoneal carbon dioxide insufflation may lead to respiratory acidosis, increased ventilation requirements, and possible serious cardiovascular compromise. The relationship between increased carbon dioxide excretion (VCO2) and intraperitoneal carbon dioxide insufflation pressure has not been well defined. METHODS: In 12 anesthesized pigs instrumented for laparoscopic surgery, intraperitoneal carbon dioxide (n = 6) or helium (n = 6) insufflation pressure was increased in steps, and VCO2 (metabolic cart), dead space, and hemodynamics were measured during constant minute ventilation. RESULTS: VCO2 increases rapidly as intraperitoneal insufflation pressure increases from 0 to 10 mmHg; but from 10 to 25 mmHg, VCO2 does not increase much further. PaCO2 increases continuously as intraperitoneal insufflation pressure increases from 0 to 25 mmHg. Hemodynamic parameters remained stable. CONCLUSIONS: By considering Fick's law of diffusion, the initial increase in VCO2 is likely accounted for by increasing peritoneal surface area exposed during insufflation. The continued increase in PaCO2 without a corresponding increase in VCO2 is accounted for by increasing respiratory dead space.

Absorption↗

PubMed1994

No differences in hemodynamics, ventricular function, and oxygen delivery in septic and nonseptic patients with the adult respiratory distress syndrome.

OBJECTIVE: To determine whether there are differences in hemodynamics, ventricular function, oxygen delivery, and oxygen consumption between septic and nonseptic patients who have the adult respiratory distress syndrome (ARDS). DESIGN: Cohort analytic study. SETTING: Tertiary care medical and surgical intensive care unit, university hospital. PATIENTS: Eighteen septic (survivors, n = 8; nonsurvivors, n = 10) and 14 nonseptic (survivors, n = 7; nonsurvivors, n = 7) patients studied within 24 hrs of the diagnosis of ARDS. INTERVENTIONS: Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen delivery and consumption measurements. MEASUREMENTS AND MAIN RESULTS: Cardiac index, right and left ventricular ejection fractions, end-diastolic volume indices, oxygen delivery, and oxygen consumption were measured. There were no differences in mean systemic and pulmonary arterial pressures, cardiac index, systemic vascular resistance, right and left ventricular ejection fractions, end-diastolic volumes, and oxygen delivery and consumption between septic and nonseptic patients. CONCLUSIONS: Early in the course of ARDS, there were no differences in hemodynamics, ventricular function, and oxygen delivery and consumption between septic and nonseptic patients. Sepsis does not account for the previously reported differences in hemodynamics, ventricular function, and oxygen delivery and oxygen consumption between survivors and non-survivors of ARDS. We speculate that both ARDS and sepsis cause release of mediators which cause similar changes in hemodynamics, ventricular function, and oxygen delivery and consumption.

Adult↗

PubMed1994

Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs.

Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor.

Animals↗

PubMed1994

Tumor necrosis factor alpha decreases in vivo diaphragm contractility in dogs.

In this study, we hypothesized that tumor necrosis factor alpha (TNF alpha) is an important mediator of sepsis-related impairment in diaphragm contractility (1-2). In 12 anesthetized, ventilated dogs, bipolar stimulating electrodes were placed on the phrenic nerves and diaphragm electromyographic activity (EMG) and shortening were recorded with needle electrodes and piezoelectric crystals, respectively. Transdiaphragmatic pressure (Pdi) was also recorded using esophageal (Pes) and abdominal balloon catheters (Pdi = Pab-Pes). Dogs were randomized to receive saline injection (n = 6), or TNF alpha 60 micrograms/kg (n = 6). All parameters were recorded hourly for 6 h. Mean arterial blood pressure decreased 1 h after infusion in TNF alpha animals (p < 0.05) with no significant change thereafter. Cardiac output increased early after TNF alpha infusion (p < 0.05) and remained at greater than baseline values at study termination. Diaphragm pressure generation and costal shortening decreased progressively from 3 to 6 h post TNF alpha infusion (p < 0.05) with no significant change in control animals. Compound diaphragm action potential in response to supramaximal phrenic stimulation decreased in TNF alpha animals (p < 0.01) with no significant change in control animals 3 and 6 h postinfusion. We conclude that TNF alpha infusion was associated with significant declines in isotonic and quasi-isometric diaphragm contraction and that this could be explained, at least in part, by impaired neuromuscular transmission.

Action Potentials↗

PubMed1993

Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans.

OBJECTIVES: To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. DESIGN: Cohort analytic study, consecutive sample. SETTING: Two tertiary care medical and surgical intensive care units in university hospitals. PATIENTS: Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. METHODS AND INTERVENTIONS: The O2 consumption (determined by indirect calorimetry), O2 delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5- to 20-minute intervals while life support was discontinued. MAIN OUTCOME MEASURES: Critical O2 delivery, critical O2 extraction ratio, and maximal O2 extraction ratio. RESULTS: In all septic and eight nonseptic patients, O2 delivery and O2 consumption displayed a biphasic relationship over the range of O2 delivery studied. There were no differences in critical O2 delivery threshold (3.8 +/- 1.5 vs 4.5 +/- 1.3 mL.min-1 x kg-1; P > .28), critical O2 extraction ratio (0.61 +/- 0.05 vs 0.59 +/- 0.16; P > .64), and maximal O2 extraction ratio (0.74 +/- 0.08 vs 0.80 +/- 0.11; P > .29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL.min-1 x kg-1 in the critical O2 delivery and 0.1 in the critical and maximal O2 extraction ratios between the septic and nonseptic groups. CONCLUSIONS: The critical O2 delivery for anaerobic metabolism was identified from the biphasic relationship between O2 delivery and O2 consumption in individual humans. The critical O2 delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O2 delivery for anaerobic metabolism or tissue O2 extraction ability. Interventions to increase O2 delivery to supranormal levels in critically ill humans in the hope of increasing O2 consumption may be inappropriate.

Adult↗

PubMed1993

Bicarbonate does not increase left ventricular contractility during L-lactic acidemia in pigs.

Lactic acidosis decreases left ventricular contractility, but whether bicarbonate increases left ventricular contractility during lactic acidosis in vivo is controversial. Therefore, we measured hemodynamics and left ventricular mechanics before and after bicarbonate administration during L-lactic acid infusion in 15 anesthetized pigs. The pigs were beta-blocked and atrially paced to minimize indirect effects of acidosis on contractility. We measured mean arterial pressure, left ventricular end-diastolic pressure, thermodilution cardiac output, left ventricular pressure (Miller catheter), and left ventricular volume (three orthogonal pairs of ultrasonic crystals). Left ventricular contractility was assessed primarily using the slope (Emax) of the end-systolic pressure-volume relationship. While PCO2 was kept constant, 0.2 M L-lactic acid was infused, which reduced arterial pH to 7.05 +/- 0.06. Animals were then randomized to receive either 1 M NaHCO3 (n = 8), which increased pH to 7.45 +/- 0.11, or an equivalent amount of 1 M NaCl (n = 7). Bicarbonate decreased mean arterial pressure (105 +/- 20 to 95 +/- 39 mm Hg, p < 0.05) but did not increase cardiac output. These effects were not significantly different from the effects of saline. Bicarbonate did not significantly increase Emax (4.2 +/- 0.8 to 4.9 +/- 0.8 mm Hg/ml) and was indistinguishable from saline (5.0 +/- 0.7 to 5.2 +/- 0.7 mm Hg/ml). We conclude that bicarbonate infusion does not directly increase left ventricular contractility during lactic acidemia in pigs within this pH range.

Acidosis, Lactic↗

PubMed1992

Plasma ionized calcium and blood lactate concentrations are inversely associated in human lactic acidosis.

Plasma ionized calcium [Ca++] concentrations are decreased in patients having lactic acidosis. To further investigate this observation, we prospectively studied nine critically ill patients who had lactic acidosis and measured arterial pH, PCO2, [Ca++], lactate, and albumin concentrations. We found a strong association between decreased [Ca++] and increased plasma lactate concentrations (r2 = 0.78, p less than or equal to 0.001). This unexpected association--[Ca++] usually increases with increasing acidosis--might be clinically important and the mechanism deserves further investigation.

Acidosis, Lactic↗

PubMed1992

Low-dose dopamine hastens onset of gut ischemia in a porcine model of hemorrhagic shock.

Gut metabolism may become anaerobic before the whole body during progressive phlebotomy in dogs. Because dopamine has selective mesenteric vasodilator effects, we asked whether dopamine could delay onset of bowel ischemia during hemorrhagic shock. We studied whole body and gut O2 consumption (VO2) and O2 delivery (QO2) using progressive phlebotomy in anesthetized pigs. Nine pigs received a dopamine infusion of 2 micrograms.kg-1.min-1, whereas a control group of seven pigs received equivalent saline infusion. Onset of ischemia in whole body and gut was determined as critical O2 delivery (QO2c), the intersection point of biphasic regression on plots of VO2-QO2 relationships. Blood flow and O2 extraction were measured as mechanisms of gut ischemia for entire in situ small and large gut using a superior mesenteric venous fistula. Dopamine hastened onset of gut ischemia relative to onset of whole body ischemia (gut critical point in terms of whole body QO2 9.9 +/- 2.1 ml O2.kg-1.min-1, whole body QO2c 7.8 +/- 0.7 ml O2.kg-1.min-1, P less than 0.01). In contrast, onset of gut ischemia in control animals occurred at same time as onset of whole body ischemia (gut critical point in terms of whole body QO2 7.4 +/- 2.3 ml O2.kg-1.min-1, whole body QO2c 7.1 +/- 2.7 ml O2.kg-1.min-1, P = not significant). Hastening of onset of gut ischemia in dopamine-treated animals was associated with decreased ability of gut to extract O2. Low-dose dopamine was not protective against gut ischemia during shock but rather caused earlier onset of gut ischemia during hemorrhagic shock.

Animals↗

PubMed1992

Histamine decreases left ventricular contractility in normal human subjects.

To determine whether histamine alters human left ventricular contractility we measured heart rate, calibrated carotid arterial pressure, and left ventricular dimensions (echocardiogram) in nine healthy volunteers. We assessed baseline contractility using the end-systolic pressure-dimension relationship and the end-systolic meridional wall stress-rate-corrected velocity of circumferential fiber shortening relationship determined over a wide range of afterloads using phenylephrine and nitroprusside infusions. We then infused histamine for 3-5 min at a dose predetermined to decrease mean arterial pressure by 20%, both before and after H1 receptor antagonist pretreatment (diphenhydramine 50 mg i.v.). Histamine decreased end-systolic pressure but, unlike an equally hypotensive infusion of nitroprusside, did not decrease end-systolic dimension or increase fractional shortening. Histamine also decreased velocity of circumferential fiber shortening at the same end-systolic meridional wall stress as controls (P < 0.05). These effects of histamine were inhibited by H1 antagonist pretreatment. We conclude that the dominant effect of histamine on the human heart is to decrease left ventricular contractility and that this decrease in contractility is dependent, at least partially, on H1-receptor activation.

Adult↗

PubMed1991

Diastolic stiffness impairs left ventricular function during hypovolemic shock in pigs.

To determine the causes of impaired left ventricular function during hypovolemic shock we measured diastolic and end-systolic pressure-volume relationships and hemodynamics. Left ventricular pressure (Millar catheter) and volume (3 ultrasonic crystal pairs) were measured in six open-chest, chloralose-morphine anesthetized, juvenile pigs. After baseline measurements, the pigs were bled and maintained at a mean aortic pressure of 50 cmH2O for 7 +/- 1 h. After resuscitation with all shed blood, left ventricular function was markedly impaired as indicated by increased end-diastolic pressure (20.3 vs. 8.7 cmH2O at baseline, P less than 0.05), decreased aortic pressure (36% of baseline, P less than 0.01), and decreased stroke volume (50% of baseline, P less than 0.01). Systolic contractility was increased (P less than 0.05), but diastolic compliance was greatly reduced due to decreased diastolic maximum (52% of baseline, P less than 0.01) and equilibrium volumes (57% of baseline, P less than 0.01). We conclude that impaired left ventricular function during hypovolemic shock is due entirely to increased diastolic stiffness. These results can theoretically be accounted for by a 20% reduction in myocardial muscle length with no change in muscle stress-strain characteristics. This may be the physiological expression of morphologically observed myocardial "zonal lesions" of hypovolemic shock.

Animals↗