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Biomedical subjects

M Mathru

Publications and source records attributed to M Mathru.

At least 19 recordsLinked to original sources
PubMed2001

Effects of profound anemia on brain tissue oxygen tension, carbon dioxide tension, and pH in rabbits.

This study sought to determine the maximum tolerable limit of anemia for the brain during halothane anesthesia. Using a multiparameter sensor, we continuously monitored brain tissue oxygen tension (PO2), carbon dioxide tension (PCO2), and pH during profound hemodilution and subsequent transfusion. Twelve New Zealand White rabbits were anesthetized, intubated, and mechanically ventilated at a fraction of inspired oxygen (FiO2) of 21% to produce an arterial carbon dioxide tension (PaCO2) of 35 to 40 mm Hg. The femoral artery was cannulated to continuously monitor arterial blood pressure and to intermittently measure arterial blood gases. The electroencephalogram (EEG) was recorded throughout the course of the study. A fiberoptic sensor was inserted into the brain for the continuous measurement of brain PO2, PCO2, pH, and temperature. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Severe anemia was induced by repeatedly withdrawing 50-mL aliquots of blood and infusing an equal volume of 6% hetastarch. This procedure was performed four times for each rabbit. After the forth blood draw and fluid infusion, a total of 60 mL of packed red blood cells were transfused. Upon completion of the hemodilution, the hemoglobin concentration was 2.4 +/- 0.3 g/dL (mean +/- SEM). Brain tissue PO2 decreased from 27 +/- 3 mm Hg to a minimum of 12 +/- 2 mm Hg. Brain tissue pH also decreased from 7.22 +/- 0.03 to 7.12 +/- 0.05 and returned to the baseline value with transfusion. Brain PCO2 did not change significantly during the experiment. Cerebral blood flow increased from 37 +/- 3 to 66 +/- 15 mL x 100 g(-1) x min(-1) during hemodilution and returned to baseline after infusion of red blood cells. There was some loss of EEG amplitude and the calculated cerebral metabolic rate (CMRO2) decreased from 4.3 +/- 0.6 to 1.9 +/- 0.3 mL x 100 g(-1) x min(-1) at the most profound level of anemia. This is the first report of which the authors are aware of continuous monitoring of brain tissue pH, PCO2, and PO2 during profound hemodilution and transfusion. Hemodilution results in a decrease in brain tissue PO2. Increases in CBF and oxygen extraction can only partially compensate for the decreased oxygen carrying capacity of the blood. Decreases in brain tissue PO2, pH, CMRO2, and a loss of EEG amplitude suggest that the maximum tolerable limit of hemodilution was achieved in this study.

Anemia↗
PubMed2000

beta-adrenergic desensitization after burn excision not affected by the use of epinephrine to limit blood loss.

BACKGROUND: Burn patients have impaired myocardial function and decreased beta-adrenergic responsiveness. Further beta-adrenergic dysfunction from systemic absorption of topically administered epinephrine that is given to limit blood loss during burn excision could affect perioperative management. The authors evaluated the effect of topical epinephrine administration to patients during burn excision on the lymphocytic beta-adrenergic response. METHODS: Fifty-five patients (age, 2-18 yr) with 20-90% body surface area burns received a standardized anesthetic for a burn excision procedure. Lymphocyte samples were taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or thrombin (controls, n = 12). Plasma epinephrine levels were measured by high-performance liquid chromatography. Lymphocyte beta-adrenergic responsiveness was assessed by measuring production of cyclic adenosine monophosphate (cAMP) after stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. beta-adrenergic receptor binding assays using iodopindolol and CGP12177 yielded beta-adrenergic receptor density. RESULTS: Epinephrine levels were elevated at 1 h (P < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients. Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients receiving epinephrine than in control patients on stimulation with isoproterenol (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration, production of cAMP decreased when compared with baseline in both control patients and those receiving epinephrine after stimulation with isoproterenol (P < 0. 05), PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic beta-adrenergic receptor content was not changed. CONCLUSIONS: Topical epinephrine to limit blood loss during burn excision resulted in significant systemic absorption and increased plasma epinephrine levels. Acute sensitization of the lymphocytic beta-adrenergic cascade was induced by the administration of epinephrine reflected by increased cAMP production after stimulation with isoproterenol and PGE1. The lymphocytic beta-adrenergic cascade exhibited homologous and heterologous desensitization 3 h after the use of epinephrine or thrombin, indicating that epinephrine administration was not a causative factor.

Administration, Topical↗
PubMed1999

A novel approach to monitor tissue perfusion: bladder mucosal PCO2, PO2, and pHi during ischemia and reperfusion.

PURPOSE: The purpose of this study is to determine if monitoring urinary bladder PCO2, PO2, and calculated intramucosal pH would be a reliable index of tissue perfusion. MATERIALS AND METHODS: This nonrandomized controlled study was conducted in a laboratory at a university medical center. Eight immature female Yorkshire pigs were studied with T-9 aortic cross-clamping for 30 minutes followed by a 60-minute period of reperfusion. Cystotomy was performed for placement of a Foley catheter and Paratrend 7 O2/CO2 sensor. RESULTS: Baseline hemodynamic and metabolic measurements were obtained along with measurements of bladder mucosal PO2 and PCO2 (mean+/-SEM). Blood flow measured with microspheres confirmed absence of blood flow during occlusion and hyperemia during reperfusion. Bladder mucosal PO2 decreased from 42+/-14.0 mm Hg (5.6 kPa) to 1.3+/-1.3 mm Hg (1.4 kPa) during the 30-minute interval of ischemia. This was followed by an increase of bladder PO2 to greater than baseline values at the end of the reperfusion period. Bladder mucosal Pco2 increased from 57+/-4.7 mm Hg (7.6 kPa) to 117+/-7.1 mm Hg (15.6 kPa) (P < .05) during ischemia. During reperfusion the Pco2 returned to baseline levels (55+/-4.0 mm Hg [7.3 kPa]). Calculated bladder mucosal pHi declined from 7.31+/-0.04 to 7.08+/-0.05 (P < .05) during the ischemic period and after reperfusion pHi was 7.17+/-0.03. CONCLUSIONS: Monitoring urinary bladder PO2, PCO2, or calculating pHi may provide a simple and reliable means of monitoring tissue perfusion.

Animals↗
PubMed1998

Continuous recordings of mixed venous oxygen saturation during weaning from mechanical ventilation and the ramifications thereof.

To define the importance of hemodynamic performance and global tissue oxygenation in determining weaning outcome, we recorded mixed venous oxygen saturation (SvO2) continuously in eight ventilator-supported patients who failed a trial of spontaneous breathing and 11 patients who tolerated a trial and were successfully extubated. Immediately before the weaning trial, SvO2 was not statistically different in the two groups (p = 0.28). On discontinuation of the ventilator, SvO2 fell progressively in the failure group (p < 0.01), whereas it did not change in the success group. During the trial of spontaneous breathing, O2 demand was similar in the two groups, but it differed in the manner with which it was met. The success group demonstrated an increase in cardiac index (p < 0.05) and O2 transport (p < 0.02). The failure group did not increase O2 transport, partly because of elevations in right- and left-ventricular afterload, but, instead, increased O2 extraction ratio (p < 0.02) with a consequent fall in SvO2. In turn, the low SvO2 combined with greater venous admixture (p < 0.0006) led to rapid arterial desaturation (p < 0.006) and a relative decrease in O2 being supplied to the tissues. In conclusion, ventilator-supported patients who failed a trial of spontaneous breathing developed a progressive decrease in SvO2 caused by the combination of a relative decrease in convective O2 transport and an increase in O2 extraction by the tissues.

Aged↗
PubMed1997

Hemodynamic effects of isovolemic hemodilution during descending thoracic aortic cross clamping and lower torso reperfusion.

BACKGROUND: Isovolemic hemodilution has been suggested for blood conservation and to improve hemodynamic tolerance to abdominal aortic cross clamping. However, the hemodynamic effects of hemodilution during descending thoracic aortic cross clamping (DAC) have not been established. We evaluated them in anesthetized swine. METHODS: Hemodilution (n = 7) was produced by the isovolemic exchange of blood for 6% hetastarch to a target hematocrit of 20%. Hematocrit in control pigs (n = 7) remained at 30%. DAC was performed at the T9 level for 45 minutes. During a 60-minute reperfusion period, control pigs were infused with lactated Ringer's solution; shed blood was returned to hemodilution pigs, followed by lactated Ringer's. If hypotension occurred despite left atrial pressure of 10 mm Hg or greater, boluses of phenylephrine were given to keep mean arterial pressure above 60 mm Hg. RESULTS: Hemodilution caused a marked reduction in hematocrit and in global oxygen delivery (DO2). DAC produced a significant increase in proximal arterial pressure, cardiac index, and DO2 and oxygen consumption (VO2) was markedly reduced in both groups. A significant increase in systemic vascular resistance during DAC occurred only in control pigs. After reperfusion, vascular resistance was significantly lower than baseline in hemodilution pigs, requiring a sixfold greater dose of phenylephrine to avoid hypotension. A lower global DO2 and supply-limited VO2 were also observed in hemodilution pigs. CONCLUSIONS: Isovolemic hemodilution maintains hemodynamic stability during DAC. During lower torso reperfusion, however, hemodilution caused hemodynamic instability, decreased global DO2, and limited VO2, which may offset its potential benefits.

Animals↗
PubMed1997

Pulmonary hypertension and systemic vasoconstriction may offset the benefits of acellular hemoglobin blood substitutes.

OBJECTIVE: We tested the hypothesis that the pharmacologic properties of a small volume of alpha alpha-cross-linked hemoglobin (alpha alpha Hb) could effectively resuscitate pigs subjected to hemorrhage. METHODS: Fourteen pigs hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg for 60 minutes were treated with a 4-mL/kg 2-minute infusion of 10 g/dL alpha alpha Hb or 7 g/dL human serum albumin, an oncotically matched control solution. RESULTS: The removal of blood (17 +/- 1.5 mL/kg) caused the typical physiologic responses to hemorrhagic hypovolemia. Infusion of alpha alpha Hb restored mean arterial pressure and coronary perfusion pressure, but cardiac output and mixed venous O2 saturation did not improve significantly. Pulmonary arterial pressure and pulmonary vascular resistance increased markedly and were higher than baseline levels after alpha alpha Hb. Infusion of human serum albumin produced only minor hemodynamic changes. Brain blood flow did improve to baseline values after alpha alpha Hb, but was the only tissue to do so. In the human serum albumin group, superior mesenteric artery blood flow recovered to baseline values, whereas brain blood flow did not. Blood flows to other tissues were similar in both groups. CONCLUSION: Small-volume infusion of alpha alpha Hb restored mean arterial pressure and brain blood flow, but pulmonary hypertension and low peripheral perfusion may offset benefits for trauma patients.

Albumins↗
PubMed1997

Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results.

BACKGROUND: In order to test the hypothesis that inhaled nitric oxide (NO) reverses the pulmonary hypertension induced by alphaalpha-diaspirin crosslinked hemoglobin (alphaalphaHb), were studied anesthetized pigs that were administered with a total dose of 200 mg/kg of 10% alphaalphaHb. Inhaled NO (5 ppm) was administered for 10 min, and then discontinued for 10 min. This cycle was then repeated with 10 ppm inhaled NO. RESULTS: alphaalphaHb caused pulmonary arterial pressure (PAP) to increase from 27 +/- 1.7 to 40 +/- 3.0 mmHg (P<0.05) and dynamic lung compliance to decrease from 29+/- 1.5 to 23+/- 1.6 ml/cmH2O (P < 0.05). After both doses of inhaled NO, but particularly 10 ppm, PAP was reduced (P < 0.05) and lung compliance increased (P < 0.05) from the alphaalphaHb levels. When inhaled NO was discontinued PAP again increased and lung compliance decreased to levels significantly different from baseline (P < 0.05). CONCLUSION: We conclude that cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance can be selectively counteracted by inhaled NO.

Journal Article↗
PubMed1996

Tourniquet-induced exsanguination in patients requiring lower limb surgery. An ischemia-reperfusion model of oxidant and antioxidant metabolism.

BACKGROUND: Surgically induced ischemia and reperfusion is frequently accompanied by local and remote organ injury. It was hypothesized that this procedure may produce injurious oxidants such as hydrogen peroxide (H2O2), which, if unscavenged, will generate the highly toxic hydroxyl radical (.OH). Accordingly, it was proposed that tourniquet-induced exsanguination for limb surgery may be a useful ischemia-reperfusion model to investigate the presence of oxidants, particularly H2O2. METHODS: In ten patients undergoing knee surgery, catheters were placed in the femoral vein of the limb operated on for collection of local blood and in a vein of the arm for sampling of systemic blood. Tourniquet-induced limb exsanguination was induced for about 2 h. After tourniquet release (reperfusion), blood samples were collected during a 2-h period for measurement of H2O2, xanthine oxidase activity, xanthine, uric acid (UA), glutathione, and glutathione disulfide. RESULTS: At 30 s of reperfusion, H2O2 concentrations increased (approximately 90%) from 133 +/- 5 to 248 +/- 8 nmol.ml-1 (P < 0.05) in local blood samples, but no change was evident in systemic blood. However, in both local and systemic blood, xanthine oxidase activity increased approximately 90% (1.91 +/- 0.07 to 3.93 +/- 0.41 and 2.19 +/- 0.07 to 3.57 +/- 0.12 nmol UA.ml-1.min-1, respectively) as did glutathione concentrations (1.27 +/- 0.04 to 2.69 +/- 0.14 and 1.27 +/- 0.03 to 2.43 +/- 0.13 mumol.ml-1, respectively). At 5 min reperfusion, in local blood, H2O2 concentrations and xanthine oxidase activity peaked at 796 +/- 38 nmol.ml-1 (approximately 500%) and 11.69 +/- 1.46 nmol UA.ml-1.min-1 (approximately 520%), respectively. In local blood, xanthine and UA increased from 1.49 +/- 0.07 to 8.36 +/- 0.33 nmol.ml-1 and 2.69 +/- 0.16 to 3.90 +/- 0.18 mumol.ml-1, respectively, whereas glutathione and glutathione disulfide increased to 5.13 +/- 0.36 mumol.ml-1 and 0.514 +/- 0.092 nmol.ml-1, respectively. In systemic blood, xanthine oxidase activity peaked at 4.75 +/- 0.20 UA nmol.ml-1.min-1. At 10 min reperfusion, local blood glutathione and UA peaked at 7.08 +/- 0.46 mumol.ml-1 and 4.67 +/- 0.26 mumol.ml-1, respectively, while the other metabolites decreased significantly toward pretourniquet levels. From 20 to 120 min, most metabolites returned to pretourniquet levels; however, local and systemic blood xanthine oxidase activity remained increased 3.76 +/- 0.29 and 3.57 +/- 0.37 nmol UA.ml-1.min-1, respectively. Systemic blood H2O2 was never increased during the study. During the burst period (approximately 5-10 min), local blood H2O2 concentrations and xanthine oxidase activities were highly correlated (r = 0.999). CONCLUSIONS: These studies suggest that tourniquet-induced exsanguination for limb surgery is a significant source for toxic oxygen production in the form of H2O2 and that xanthine oxidase is probably the H2O2-generating enzyme that is formed during the ischemia-reperfusion event. In contrast to the reperfused leg, the absence of H2O2 in arm blood demonstrated a balanced oxidant scavenging in the systemic circulation, despite the persistent increase in systemic xanthine oxidase activity.

Adult↗
PubMed1996

Magnetic resonance imaging of the upper airway. Effects of propofol anesthesia and nasal continuous positive airway pressure in humans.

BACKGROUND: Anesthetic agents inhibit the respiratory activity of upper airway muscles more than the diaphragm, creating a potential for narrowing or complete closure of the pharyngeal airway during anesthesia. Because the underlying mechanisms leading to airway obstruction in sleep apnea and during anesthesia are similar, it was hypothesized that anesthesia-induced pharyngeal narrowing could be counteracted by applying nasal continuous positive airway pressure (CPAP). METHODS: Anesthesia was induced in ten healthy volunteers (aged 25-34 yr) by intravenous administration of propofol in 50-mg increments every 30-s to a maximum of 300 mg. Magnetic resonance images of the upper airway (slice thickness of 5 mm or less) were obtained in the awake state, during propofol anesthesia, and during administration of propofol plus 10 cm nasal CPAP. RESULTS: Minimum anteroposterior diameter of the pharynx at the level of the soft palate decreased from 6.6 +/- 2.2 mm (SD) in the awake state to 2.7 +/- 1.5 mm (P < 0.05) during propofol anesthesia and increased to 8.43 +/- 2.5 mm (P < 0.05) after nasal CPAP application. Anteroposterior diameter of the pharynx at the level of the dorsum of the tongue increased from 7.9 +/- 3.5 mm during propofol anesthesia to 12.9 +/- 3.6 mm (P < 0.05) after nasal CPAP. Pharyngeal volume (from the tip of the epiglottis to the tip of the soft palate, assuming this space to be a truncated cone) significantly increased from 2,437 +/- 1,008 mm3 during propofol anesthesia to 5,847 +/- 2,827 mm3 (P < 0.05) after nasal CPAP application. CONCLUSIONS: In contrast to the traditional view that relaxation of the tongue causes airway obstruction, this study suggests that airway closure occurs at the level of the soft palate. Application of nasal CPAP can counteract an anesthesia-induced pharyngeal narrowing by functioning as a pneumatic splint. This is supported by the observed reduction in anteroposterior diameter at the level of the soft palate during propofol anesthesia and the subsequent increase in this measurement during nasal CPAP application.

Adult↗
PubMed1996

Effect of jet ventilation on heart failure: decreased afterload but negative response in left ventricular end-systolic pressure-volume function.

OBJECTIVE: To examine the mechanism of cardiac assist with systolic jet ventilation, specifically effects on loading conditions and left ventricular pressure-volume function. Both systolic and diastolic jet ventilation were compared in the absence and presence of heart failure. DESIGN: Prospective, two-factor, repeated-measures study. SETTING: Animal laboratory. SUBJECTS: Ten anesthetized, closed-chest dogs. INTERVENTIONS: The measurement protocol consisted of two phases: a) apnea, randomized jet ventilation (systole- and diastole-synchronized); b) postjet ventilation apnea, before and after heart failure, induced with a propranolol-imipramine-plasma expansion treatment. MEASUREMENT AND MAIN RESULTS: Systolic and diastolic jet ventilation was associated with mean airway pressures of approximately 7 mm Hg and intrapleural pressures of approximately 3 mm Hg in both heart conditions. In normal hearts, jet ventilation (either mode) decreased transmural left ventricular end-diastolic pressure by 40% to 60% (p < .05), left ventricular end-diastolic volume 25 +/- 8%, and stroke volume by 28% to 30%. Heart failure was associated with decreases (41 +/- 6%) in end-systolic pressure-volume function (i.e., pressure change/volume change or elastance), transmural left ventricular end-systolic pressure (22 +/- 3%), and stroke volume (16 +/- 4%), and increased transmural left ventricular end-diastolic pressure (139 +/- 6%). Application of jet ventilation (either mode) during heart failure did not affect stroke volume but significantly (p < .05) attenuated transmural left ventricular end-diastolic pressure by 30% to 40%, left ventricular end-diastolic volumes by 33 +/- 9%, and transmural left ventricular end-systolic pressure by 11% to 19% (p < .05). After jet ventilation, left ventricular elastance was decreased 36 +/- 8% in normal hearts and 35 +/- 11% in failing hearts. Stroke volume, however, returned to baseline levels because of increases in transmural left ventricular end-diastolic pressure in both heart conditions, and also in failing hearts, because transmural left ventricular end-systolic pressure remained decreased approximately 30% (p < .05). CONCLUSIONS: Jet ventilation did not decrease stroke volume in failing hearts because of the afterload-reducing benefit (decreased transmural left ventricular end-systolic pressure) of increased intrapleural pressure in dilated ventricles. Moreover, jet ventilation did not have positive effects on myocardial function and had negative effects on left ventricular elastance in the postjet ventilation period in both normal and failing hearts. Cardiac assist by jet ventilation was not cycle specific, suggesting no selective benefit of jet ventilation over conventional positive-pressure ventilation during heart failure. These studies demonstrate a negative inotropy associated with jet ventilation that, during heart failure, may compromise the general benefit of positive-pressure-mediated increases in intrapleural pressure.

Adrenergic Uptake Inhibitors↗
PubMed1994

Urine hydrogen peroxide during adult respiratory distress syndrome in patients with and without sepsis.

BACKGROUND: The lung injury in adult respiratory distress syndrome (ARDS) has been associated with increased expiratory hydrogen peroxide (H2O2) concentrations. Furthermore, patients with sepsis and ARDS are reported to have greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized that the systemic presence of H2O2 would be detectable in the urine of these two groups of patients and that, in the case of ARDS sepsis, the relative contribution of each disease to the production this analyte would be discernible. Accordingly, we used an in vitro radioisotope assay to follow the weekly course of urine H2O2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary catheters and in samples provided by healthy volunteers. METHODS: Thirty patients with ARDS were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling catheter was used to collect urine from each patient over a 24-h period, first within 48 h of ICU admission and then every seventh day over the course of their illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha-ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h period following a 5-day minimum with an indwelling urinary catheter. RESULTS: Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7) was significantly higher than that in patients who survived sepsis (352 +/- 14 mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group remained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30 mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS-sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy donors and patients without ARDS). CONCLUSION: Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS only during the first 10 days in the ICU; however, urine H2O2 levels were significantly greater in the patients with ARDS and sepsis. Moreover, despite no initial difference in lung injury, patients who did not survive ARDS and sepsis had consistently greater urine H2O2 concentration than patients who survived sepsis. The urine H2O2 level in the ARDS-only group was about 70 percent of the level in the survivor ARDS and sepsis group, suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes during combined ARDS and sepsis. Furthermore, these studies demonstrate that urine H2O2 may be a useful analyte to differentiate the severity of oxidant processes in patients with ARDS and sepsis albeit the prognosis appears to be survival or nonsurvival.

Adolescent↗
PubMed1994

Measurement of right ventricular volume in human explanted hearts using ultrafast cine computed tomography.

The quantitative measurement of right ventricular (RV) volume has been attempted by a number of methods, including nuclear magnetic resonance imaging, contrast angiography, echocardiography, and radionuclide angiography. All of these methods have limitations. Ultrafast cine computed tomographic (CT) scan is a new technology that may have an important role in on-line ventricular volume measurements. Twelve human explanted hearts, fixed in formalin, were subjected to ultrafast cine CT scans to estimate RV volume. The volumes derived from the CT scans were compared with actual fluid volumes needed to fill the RV volume measurements. All measurements were conducted independently by two observers. Actual RV volumes in the 12 hearts ranged from 29.8 ml to 174.6 ml. A strongly significant correlation between actual volume and CT volume was seen (r = 0.99). Agreement between observers was also seen to be highly significant (r = 0.992). Limitations to accurate in vivo assessment due to bolus injection of contrast medium might include alterations in ventricular pressure change. Similarly, differentiation of the endocardial border with contrast may not be as sharp as that with an air-tissue interface. This study demonstrates that RV volumes can be reliably determined by ultrafast cine CT scans in explanted hearts. On-line systolic and diastolic volumes and thus stroke volume, ejection fraction, etc, can be accurately defined independent of cardiac orientation. This technique offers opportunities to study ventricular function under various conditions.

Cardiac Volume↗
PubMed1993

Effects of fentanyl on coronary blood flow distribution and myocardial oxygen consumption in the dog.

Little data exist on the effects of fentanyl on coronary blood flow (CBF), myocardial oxygen balance, and the regional distribution of blood flow. These studies were designed to determine whether fentanyl had any intrinsic effects on myocardial oxygen consumption (MVO2) and blood flow distribution. In anesthetized dogs, fentanyl was administered in a dose of 50 micrograms/kg and various measurements were made at 5 and 20 minutes. After hemodynamic recovery from the fentanyl, the animals were treated with atropine to block the known vagomimetic effect of fentanyl and challenged with acetylcholine (3.5 micrograms/kg); then fentanyl (50 micrograms/kg) was again administered and measurements made at 5 and 20 minutes. In the untreated dogs at 5 minutes post-fentanyl, heart rate (HR) decreased 30% and at 20 minutes decreased 29%. Treatment with atropine essentially eliminated HR changes at both time periods. Mean arterial pressure (MAP) fell by 20% and 22% at 5 minutes and 20 minutes, respectively, in the untreated group, but when atropine was administered, MAP was observed to be intermediate between baseline and the untreated animals. Left ventricular MVO2 at 5 minutes in the untreated group was modestly but not significantly reduced. However, at 20 minutes post-fentanyl, MVO2 decreased significantly. MVO2 was essentially unchanged after atropine. Regional CBF (measured by radiolabelled microspheres) was unchanged at 5 minutes, but all layers exhibited significant reductions at 20 minutes. In the atropine group, only the LV epicardial area appeared to show decreases in flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1993

Hemodilution with oxyhemoglobin. Mechanism of oxygen delivery and its superaugmentation with a nitric oxide donor (sodium nitroprusside).

BACKGROUND: Hemodilution (HD) with oxyhemoglobin colloid (oxyHb) provides a greater arterial oxygen content (CaO2) than HD with conventional colloids; however, oxygen delivery (DO2) is essentially the same, because, in contrast to conventional HD, cardiac output (CO) is not augmented. This study seeks to elucidate the mechanism that limits CO during oxyHb-HD and to test whether infusion of a nitric oxide (NO) donor would augment DO2, because oxyHb is known to inactivate in vitro endothelial-derived NO. METHODS: Anesthetized dogs were isovolemically hemodiluted with 10% oxyHb, 8% albumin, or 10% methemoglobin (weak NO inactivator) to 20% hematocrit. After HD, sodium nitroprusside (SNP) was titrated intravenously until decreases (> 10 mmHg) in mean aortic pressure (Pao) indicated the presence of exogenous NO. Systemic hemodynamics and regional blood flows (microsphere method) were measured. RESULTS: Albumin-HD and metHb-HD produced typical HD-mediated responses: increased CO (63-65%), slight decreases (13-15%) in DO2, decreases in systemic vascular resistance (SVR) proportional to the decreases (49-52%) in blood viscosity of all three groups, and increased regional blood flows (RBF). Responses to oxyHb-HD were atypical: CO and its determinants were not changed, DO2 decreased (23%) proportional to CaO2, and SVR and most RBF were not changed except for a net redistribution of CO to myocardium and skeletal muscle. In albumin-HD or metHb-HD, SNP (2-5 micrograms.kg-1.min-1) induced comparable decreases in mean Pao (29-37%) and SVR (39-41%); however, CO, RBF, and DO2 were not affected. In oxyHb-HD, exceptionally large doses of SNP (54 +/- 5 micrograms.kg-1.min-1) decreased mean Pao only 19 +/- 1%; however, CO increased 78 +/- 5% and decreases (61 +/- 3%) in SVR were slightly greater than viscosity reductions. Other determinants of CO were not affected. Most RBF increased proportional to CO; there was, however, preferential distribution to myocardium and skeletal muscle. Consequently, the augmented CO, and CaO2 of oxyHb-HD, produced large increases in DO2, 77 +/- 5% from HD alone and 43 +/- 3% from prehemodilution values. CONCLUSIONS: This study indicates that the limited CO and DO2 of oxyHb-HD resulted from opposing changes in two determinants of flow, i.e., reduced blood viscosity and increased arterial resistance (vasoconstriction). The vasoconstriction was not evident with metHb-HD and was reversed by the SNP infusion, indicating that oxyHb inactivated in vivo endothelial-derived NO. The ability of the NO donor (SNP) to facilitate large viscosity-mediated increases in DO2 during oxyHb-HD is an important finding that could potentially render oxyHb colloids more useful than conventional colloids, particularly for the individual with a compromised circulation who would benefit from an increased oxygen supply.

Animals↗
PubMed1993

Separation of myocardial versus peripheral effects of calcium administration in normocalcemic and hypocalcemic states using pressure-volume (conductance) relationships.

This study used left ventricular pressure-volume (conductance) relationships to separate the effects of calcium administration on myocardial performance and peripheral vasoconstriction in normocalcemic and hypocalcemic states. Hypocalcemia was produced in anesthetized dogs with intravenous citrate-phosphate-dextrose until serum [Ca2+] was approximately 0.7 mmol/L. Calcium (CaCl2) bolus (5 mg/kg) was administered during normocalcemia (n = 6) and hypocalcemia (n = 6), and data were collected at 1, 5 and 10 min after CaCl2 administration. During normocalcemia, CaCl2 administration increased [Ca2+] 19% at 1 min and was accompanied by a 47% (P < 0.05) decrease in left ventricular contractility (i.e., end-systolic elastance or E(lves)) and a 13% (P < 0.05) increase in systemic vascular resistance. At 5 and 10 min, serum [Ca2+] and the hemodynamic variables began to return to the baseline values. During hypocalcemia, E(lves) decreased 25% (P < 0.05), but after CaCl2 bolus, it increased to baseline levels and remained there during the 10-min period. Hypocalcemia and the CaCl2 bolus did not significantly affect SVR. In conclusion, these studies suggest that the indications for the use of calcium should depend on the initial serum level of ionized calcium.

Animals↗