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Biomedical subjects

C W Buffington

Publications and source records attributed to C W Buffington.

At least 19 recordsLinked to original sources
PubMed1999

Blood pressure is maintained despite profound myocardial depression during acute bupivacaine overdose in pigs.

UNLABELLED: Bupivacaine-induced cardiovascular collapse is a feared complication because of the difficulty in restoring stable circulation (1). Early recognition is important so that the injection of bupivacaine can be discontinued. We used an animal model of near-cardiac arrest from bupivacaine infusion to identify the sequence of hemodynamic events that precedes bupivacaine-induced cardiovascular collapse. Twelve pigs (23-25 kg) were sedated with ketamine and anesthetized with halothane. Arterial blood pressure and cardiac output were measured. Bupivacaine (3.75 mg/mL) was administered at a rate of 5.73 mL/min (approximately 1 mg x kg(-1) x min(-1)) through a central venous catheter until severe ventricular arrhythmia occurred. Blood pressure and heart rate were unchanged, but cardiac output decreased by 40% with increasing doses of bupivacaine. Calculated peripheral resistance increased by 54%. The QRS complex of the surface electrocardiogram widened, and the R-wave amplitude decreased 80%, together with the decrease in cardiac output. T-wave amplitude increased initially but returned toward baseline at the largest bupivacaine doses. The plasma concentration of bupivacaine after the infusion was 16+/-6.8 microg/mL. IMPLICATIONS: The increase in vascular resistance that accompanies acute bupivacaine overdose maintains blood pressure but masks severe myocardial depression.

Anesthetics, Local↗
PubMed1998

Transmural pressure of epidural veins in the thoracic and lumbar spine of pigs.

BACKGROUND: The aim of this study was to determine the transmural pressure gradient of epidural veins located within the spinal column and to investigate the effects of increased intra-abdominal and intrathoracic pressure on this gradient. METHODS: Fourteen pigs were sedated with ketamine and anesthetized with halothane. Ventilation was controlled after tracheotomy. Needles were inserted into the epidural and subarachnoid space, and a catheter was threaded into an epidural vein. Pressures in these structures were measured during controlled and spontaneous ventilation, increased abdominal pressure, and thoracic compression. Measurements were made in both the thoracic and lumbar regions. RESULTS: The pressure gradient between the epidural vein and the surrounding epidural space was low-11 or 2 mmHg--in both the lumbar and thoracic areas. This gradient was not affected by the mode of ventilation or increased abdominal or thoracic pressure (or both), even though the absolute intramural pressure increased. CONCLUSION: The pressure gradient between the epidural vein and the surrounding space is low and does not change when abdominal or thoracic pressures are increased.

Animals↗
PubMed1996

Nitric oxide mediates hepatic cytochrome P450 dysfunction induced by endotoxin.

BACKGROUND: Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide. METHODS: Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro. RESULTS: Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97). CONCLUSIONS: Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.

Animals↗
PubMed1995

Effects of intracoronary calcium chloride on the postischemic heart in pigs.

Whether calcium chloride (CaCl2) should be used to reverse myocardial dysfunction during cardiac operations remains a controversial issue. Calcium chloride may reduce, rather than increase, myocardial contractility and may produce exaggerated vasoconstriction in postischemic vessels in which the endothelium has been damaged. These possibilities were investigated in an open-chest porcine model that allowed control of systemic hemodynamics. Incremental doses of CaCl2 (1, 3, and 10 mg/min) were infused directly into a coronary artery before and after 10 or 15 minutes of ischemia followed by 15 minutes of reperfusion. Calcium chloride increased regional contraction, coronary blood flow, and oxygen consumption before ischemia, whereas oxygen and lactate extraction were unchanged. After ischemia and reperfusion, contraction was impaired and lactate extraction was reduced, but a similar response to CaCl2 was observed. Contraction returned to baseline values promptly after CaCl2. Thus, CaCl2 exerts a positive inotropic effect both in normal and in postischemic myocardium. Calcium chloride does not cause direct coronary constriction nor does it worsen myocardial stunning after a short period of normothermic myocardial ischemia.

Analysis of Variance↗
PubMed1995

Inhaled anesthetics alter the determinants of coronary collateral blood flow in the dog.

BACKGROUND: Whether coronary steal is induced by inhaled anesthetic agents remains controversial in part because multiple factors determine collateral blood flow. METHODS: We used an established model to determine how halothane, isoflurane, and desflurane affect the hemodynamic determinants of coronary collateral blood flow. Twelve dogs were studied 4-5 weeks after ameroid constrictor implantation. Retrograde flow draining from the occluded artery was measured as an index of collateral flow after antegrade embolization. Pressure in the supplying artery at the origin of the collaterals was estimated with a stop-flow technique. These techniques allow calculation of collateral segment resistance and the resistances of the supply artery upstream and downstream from the origin of the collaterals. RESULTS: None of the inhaled anesthetics affected collateral segment resistance. Downstream (arteriolar) resistance of the supplying artery was decreased by desflurane (-45%), isoflurane (-35%), and halothane (-15%), lowering pressure at the origin of the collaterals, an effect that was partially offset by a decrease in upstream resistance. Retrograde flow was unaffected by isoflurane and halothane but decreased by about 20% during desflurane administration. CONCLUSIONS: Inhaled anesthetics have many effects on segmental resistance and pressure in the coronary circulation. These findings help explain conflicting results from previous studies and provide a useful model for investigating the effects of inhaled agents on small coronary arteries.

Anesthetics, Inhalation↗
PubMed1995

Comparison of myocardial ischemia induced by endothelin vs. mechanical stenosis in pigs.

We have determined the transmural distribution of myocardial flow and ischemia during endothelin (ET-1) infusion and compared these results with the effects of mechanical stenosis. In anesthetized pigs, coronary flow was reduced 15, 30, and 50% from baseline values with a mechanical stenosis (n = 7) or increasing doses of intracoronary ET-1 (n = 8). The inner-to-outer flow ratio decreased with decreasing total flow during mechanical stenosis, and S-T segment elevation occurred predominantly in the subendocardium. In contrast, the inner-to-outer flow ratio exceeded 1.0 and actually increased during ET-1 infusion. ET-1 limited the electrocardiographic evidence of subendocardial ischemia and attenuated contractile dysfunction compared with mechanical stenosis at the same coronary flows, even though lactate flux was similar. Reactive hyperemia was retained with ET-1, even when coronary flow was reduced enough to cause lactate production. These results demonstrate a more uniform transmural distribution of flow caused by microvascular constriction than by a large-vessel stenosis.

Animals↗
PubMed1995

Vessel tone affects transmural distribution of coronary flow during hypoperfusion.

Subendocardial flow is selectively impaired during coronary hypoperfusion. Systolic compression of intramyocardial vessels not only stops capillary flow but empties vessels as well, leading to reversed flow in the arteries that penetrate the myocardium. The tone of these vessels influences the magnitude of flow oscillation during the cardiac cycle, but whether vessel tone is an independent determinant of subendocardial perfusion during coronary hypoperfusion has not been determined. The discovery of endothelin (ET-1) has made it possible to counteract metabolic vasodilation and increase vessel tone during hypoperfusion. A shunt from a carotid artery to the left anterior descending coronary artery was installed in open-chest pigs anesthetized with halothane. Arterial pressure and heart rate were held constant, and coronary pressure was reduced in stages by restricting shunt flow during intracoronary infusion of ET-1 (n = 7) or adenosine (n = 5). Microspheres were injected at each stage to determine layer flow. Coronary resistance was two- to three-fold higher and subendocardial flow was lower at similar coronary pressures in the animals receiving ET-1 than in those receiving adenosine. In contrast, flow distribution across the left ventricular wall was more homogeneous with ET-1 than with adenosine, even at coronary pressures low enough to cause lactate production and regional hypokinesis. These results demonstrate that vessel tone has an independent effect on absolute subendocardial flow as well as transmural flow distribution during coronary hypoperfusion.

Adenosine↗
PubMed1994

Speed and sensitivity of mechanical versus electrographic indicators to mild or moderate myocardial ischemia in the pig.

BACKGROUND: Intraoperative myocardial ischemia may be detected and quantified by indexes of myocardial contraction or by electrography. The relative reliability of these two approaches is controversial. Two issues are relevant: the timing of events after the onset of mild to moderate ischemia, and the sensitivity of measures to ischemia at steady state. METHODS: In eight pigs, a carotid-to-left anterior descending coronary artery shunt with a flow meter was installed. Flow to the left anterior descending coronary artery was reduced in steps of 10% from baseline values to 50% of baseline. Wall thickness, myocardial QRS amplitude, and ST-segment deviation were measured every 1 min for 6 min at each step. Regional myocardial lactate extraction was measured at 6 min. RESULTS: Linear relations were found between the percentage of baseline coronary flow and all four dependent variables at steady state, indicating equal sensitivity (defined as rate of change with respect to flow reduction) to myocardial ischemia. After flow reduction, decreases in systolic wall thickening occurred first and were followed by a QRS amplitude decrease and then ST-segment elevation. The onset of ischemia was earlier with more severe reductions of coronary flow. CONCLUSIONS: Mechanical and electric measures of myocardial ischemia show equal sensitivity at steady state even though regional contraction changed more quickly than did QRS amplitude or the ST-segment after an abrupt reduction in coronary flow.

Animals↗
PubMed1994

Regional oxygen consumption persists in dyskinetic canine myocardium.

Regional myocardial O2 consumption was measured in anesthetized dogs both in baseline conditions and during intracoronary infusion of lidocaine, verapamil, sodium citrate, or 2,3-butanedione-monoxime (BDM). Despite regional hypokinesis and dyskinesis during drug infusion, regional O2 consumption was reduced only 30-40% by lidocaine, verapamil, and citrate and not at all by BDM. These results cast doubt on an important assumption of the "hibernation" theory: the protective matching of regional perfusion and contraction.

Animals↗
PubMed1994

Regional contraction improves, then declines after reperfusion of ischemic myocardium in the dog.

Myocardial ischemia occurs during cardiac surgery and coronary artery angioplasty. If ischemia is short-term or the heart is protected, cellular necrosis can be avoided. Nevertheless, myocardial stunning occurs and can reduce cardiac performance in the hours after ischemia. Such stunning is preceded by a short period of normal or above normal contraction immediately after reperfusion. The time course of this phenomenon was investigated in six anesthetized dogs subjected to a 10-minute total coronary occlusion. Regional contraction was measured in the ischemic zone and in a remote zone of the heart with a sonomicrometer. Remote zone contraction increased during ischemia, returned toward baseline values after reperfusion, and was stable for the next hour, indicating little effect of time on the experimental preparation. In contrast, ischemic zone contraction was abolished by 10 minutes of coronary occlusion, returned to baseline or greater levels within 1 to 3 minutes following release of the occlusion, then gradually declined over 10 to 20 minutes to a level about 40% below baseline values, indicating myocardial stunning. These findings support the notion that a honeymoon period of normal or above normal function exists during early reperfusion, and that stunning manifests later. This reperfusion "honeymoon" may create a false sense of security.

Animals↗
PubMed1993

Electromechanical association in regionally stunned swine myocardium.

BACKGROUND: Postischemic myocardial dysfunction ("stunned" myocardium) is a common problem after cardiac surgery and cardiac transplantation. A "low-voltage" QRS complex in the electrocardiogram is also often seen in patients with severe cardiac dysfunction. The authors investigated the relationship between mechanical function and electrographic characteristics in postischemic swine myocardium, and determined whether inotropic stimulation with dobutamine alters the electrogram while improving mechanical function. METHODS: Regional wall thickening and regional electrogram from electrodes in the endo- and epicardium were measured in 12 pigs during intravenous infusion of several doses of dobutamine (1-25 micrograms.kg-1.min-1) before and after 10 or 15 min of ischemia followed by 1 h of reperfusion. RESULTS: Wall thickening was abolished after ischemia and reperfusion, and QRS amplitude decreased 25% in the endocardium and 29% in the epicardium. Dobutamine infusion restored both wall thickening and myocardial QRS amplitude to baseline values. The correlation between myocardial QRS amplitude and systolic wall thickening was significant in each animal (r = 0.88 +/- 0.02 (mean +/- 1 SEM, n = 12); median r = 0.89; range 0.74-0.95, P < 0.01, for all relations). CONCLUSIONS: This study showed a close association between local electrical and mechanical events in postischemic swine myocardium.

Animals↗
PubMed1993

Regional load dependence of postischemic myocardium.

Few studies have examined how load affects the contraction of the myocardium following ischemia. We have therefore developed a canine model in which preload (left atrial pressure) and afterload (mean arterial pressure) are independently varied and heart rate is kept constant. Systolic contraction was found to increase in proportion to preload under preischemic conditions. However, postischemic systolic contractions were reduced and the response to preload was also markedly diminished. Response of systolic thickening to preload was significant in controls (p = 0.003, N = 8) but nonsignificant after 10 minutes of ischemia and 1 hour of reperfusion. Effects of inotropic stimulation were also examined. Dobutamine restored systolic thickening and myocardial contraction to baseline levels following ischemia. However, contraction following dobutamine treatment remained lower than that observed under preischemic conditions. The ideal treatment of the postischemic myocardium should provide low afterload, high heart rate, and high contractility.

Adenosine Triphosphate↗