Search PubMed⌕ Search

Biomedical subjects

B J Leone

Publications and source records attributed to B J Leone.

At least 37 records · Page 2Linked to original sources

Acute isovolemic hemodilution and blood transfusion. Effects on regional function and metabolism in myocardium with compromised coronary blood flow.

The use of isovolemic hemodilution to prevent adverse side effects of homologous blood transfusions has increased. The lowest level of hemoglobin that can be tolerated without regional myocardial dysfunction, however, had not been precisely defined for left ventricular myocardium with compromised coronary blood flow. This level was determined in our study in 19 dogs with critical stenosis of the left anterior descending coronary artery during graded isovolemic hemodilution. Regional function was assessed by sonomicrometry in the territory supplied by the left anterior descending coronary artery, as well as in two noncompromised left ventricular areas; oxygen extraction and consumption in the left anterior descending coronary artery region were assessed by analysis of anterior descending coronary venous oxygen saturation. The median lowest level of hemoglobin tolerated without contractile dysfunction of the territory supplied by the left anterior descending artery was 7.5 gm/dl, with lower and upper quartiles of 6 and 9 gm/dl. In addition to a marked increase in cardiac output and transstenotic left anterior descending flow, global cardiac and regional myocardial functions were unchanged at a hemoglobin level of 7.5 gm/dl, as compared with a control level of hemoglobin of 12.0 +/- 0.4 gm/dl. At a mean level of hemoglobin of 6.0 +/- 0.4 gm/dl, marked contractile dysfunction developed in the left anterior descending region: Systolic shortening decreased from 24.2% +/- 2.1% to 17.9% +/- 1.9% (p < 0.01); postsystolic shortening increased from 4.0% +/- 3.0% to 12.2% +/- 3.8% (p < 0.01); and in the left anterior descending region, oxygen consumption decreased. The increase of arterial level of hemoglobin by only 1.9 +/- 0.2 gm/dl restored contractile function in the left anterior descending region, regional oxygen consumption, and oxygen extraction across the left anterior descending region. Moderate isovolemic hemodilution is relatively well tolerated in left ventricular myocardium with compromised coronary blood flow, and hemodilution regional contractile dysfunction induced by hemodilution is reversible by minimal blood transfusion.

Animals↗

Warming during cardiopulmonary bypass is associated with jugular bulb desaturation.

The objective of this study was to characterize cerebral venous effluent during normothermic nonpulsatile cardiopulmonary bypass. Thirty-one (23%) of 133 patients met desaturation criteria (defined as jugular bulb venous oxygen saturation less than or equal to 50% or jugular bulb venous oxygen tension less than or equal to 25 mm Hg) during normothermic cardiopulmonary bypass (after hypothermic cardiopulmonary bypass at 27 degrees to 28 degrees C). Cerebral blood flow, calculated using xenon 133 clearance methodology, was significantly (p less than 0.005) higher in the saturated group (33.7 +/- 10.3 mL.100 g-1.min-1) than in the desaturated group (26.2 +/- 6.9 mL.100 g-1.min-1), whereas the cerebral metabolic rate for oxygen was significantly lower (p less than 0.005) in the saturated group (1.28 +/- 0.39 mL.100 g-.min-1) than in the desaturated group (1.52 +/- 0.36 mL.100 g-1.min-1) at normothermia. The arteriovenous oxygen difference at normothermia was lower in the saturated group (3.92 +/- 1.12 mL/dL) than in the desaturated group (5.97 +/- 1.05 mL/dL). Neuropsychological testing was performed in 74 of the 133 patients preoperatively and on day 7 postoperatively. There was a general decline in mean scores of all tests postoperatively in both groups with no significant difference between the groups. We conclude that cerebral venous desaturation represents a global imbalance in cerebral oxygen supply-demand that occurs during normothermic cardiopulmonary bypass and may represent transient cerebral ischemia. These episodes, however, are not associated with impared neuropsychological test performance as compared with the performance of patients with no evidence of desaturation.

Aged↗

Left ventricular regional function and relaxation: effects of inotropic stimulation.

The effects of increasing doses of two inotropes, isoproterenol and calcium chloride (CaCl2), on left ventricular regional myocardial function and isovolumic relaxation were studied in six anesthetized sheep. After baseline data, CaCl2 was given as intravenous boluses to yield doses of 10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 160 mg/kg. After a second series of baseline data were obtained, constant infusions of isoproterenol were begun with doses of 0.025 micrograms/kg/min, 0.05 micrograms/kg/min, 0.1 micrograms/kg/min, 0.2 micrograms/kg/min, and 0.4 micrograms/kg/min. During each stage of the protocol with both inotropes, data were recorded during acute constriction of the descending thoracic aorta. Left ventricular relaxation was assessed by analysis of peak negative left ventricular (LV) dP/dt and the time constant of isovolumic left ventricular relaxation (Trelax). Regional myocardial function showed little change in either apical or basal segments until high doses of the inotropes. Peak negative LV dP/dt significantly changed from baseline (775 +/- 60 mmHg/s) with 0.2 micrograms/kg/min (1780 +/- 400 mmHg/s, P < 0.05 v baseline) and 0.4 micrograms/kg/min (2,220 +/- 380 mmHg/s, P < 0.05 v baseline) of isoproterenol, and was unchanged by CaCl2. Trelax was significantly decreased by all doses of isoproterenol, whereas only one dose of CaCl2 decreased Trelax. Trelax was increased with afterloading and this effect was altered by isoproterenol. It is concluded that isoproterenol hastens, whereas CaCl2 does not alter, left ventricular relaxation. This may reflect beta-adrenergic modulation of calcium fluxes during isovolumic relaxation.

Animals↗

Validation of 133Xe clearance as a cerebral blood flow measurement technique during cardiopulmonary bypass.

133Xe clearance to measure cerebral blood flow (CBF) was examined in 10 dogs during cardiopulmonary bypass. As a reference method, a continuous Kety-Schmidt technique (CBFKS) with 133Xe as indicator was used. Extracranial tissue was removed to directly place the 133Xe detectors on the skull, and the head was covered with a 3 mm lead shield to minimize contamination of the 133Xe clearance curve with extracranial radiation. 133Xe detectors for the Kety-Schmidt technique were embedded in a shielded brass block to minimize interference with radiation from the animal's body. 133Xe clearance data were analyzed using stochastic (CBF10, CBF15, and CBFINF) and initial slope methods (CBFIS), and the results were compared with CBFKS using linear regression. CBF15 and CBFINF yielded similar CBF values as CBFKS (CBFKS = 0.97.CBF15-2.08, r = 0.92, p less than 0.01; CBFKS = 1.13.CBFINF-1.21, r = 0.92, p less than 0.01). CBF10 slightly overestimated CBFKS but still showed a close correlation to CBFKS (CBFKS = 0.89.CBF10-2.58, r = 0.92, p less than 0.01) and CBFIS considerably overestimated CBFKS (CBFKS = 0.60.CBFIS-1.27, r = 0.87, p less than 0.01). With extracranial contamination of the 133Xe clearance curve minimized, all 133Xe clearance techniques used to measure CBF were consistently related to CBFKS in a constant, significant manner. 133Xe clearance therefore is a valid method to assess CBF during cardiopulmonary bypass.

Animals↗

Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation.

OBJECTIVE: The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. METHODS: Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. RESULTS: Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. CONCLUSIONS: (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.

Animals↗

Perioperative myocardial ischemia and infarction. Prophylaxis and treatment of ischemia.

Protection from and treatment of myocardial ischemia involves detection and recognition of early changes in myocardial function associated with ischemia, as well as use of techniques and agents designed to alleviate or ameliorate ischemia. However, decisions regarding which agent(s) to employ depend upon not only the effects of a particular therapy but also the interaction(s) among the therapeutic agents and anesthetics. All the drugs and treatments discussed above may have beneficial effects in conscious patients but variable degrees of effectiveness during anesthesia. The choice of agents to be used for myocardial protection ultimately depends upon clinical decisions regarding coronary blood supply and myocardial oxygen demand. The availability of several different classes of agents capable of altering specific physiological variables allows a wide variety of clinical situations to be effectively managed.

Cardiotonic Agents↗

Effects of acute isovolemic hemodilution and anesthesia on regional function in left ventricular myocardium with compromised coronary blood flow.

The effects of progressive, isovolemic hemodilution using Dextran 70 and the effect of halothane (0.7, 0.9, 1.1, and 1.3% end-tidal, administered randomly at each level of hemodilution) on global cardiovascular and regional LV contractile functions were investigated in 24 dogs with induced critical constriction of the left anterior descending coronary artery (LAD). Two additional groups of six dogs each (with and without LAD stenosis) not undergoing hemodilution served as time controls. Regional LV contractile function was assessed by sonomicrometry in the flow-compromised apical LAD territory, as well as in three non-compromised LV areas supplied by the left circumflex coronary artery. Regional myocardial function was found to be stable throughout the study period of 4-5 h in both time control groups. Mean arterial and coronary perfusion pressures as well as LV dP/dtmin decreased (P < 0.01) during hemodilution. LV dP/dtmax remained unchanged, and heart rate and LVEDP increased slightly (P < 0.05). Systolic shortening (SS) in the LAD territory was unchanged at a hematocrit (HCT) of 33.5 +/- 0.3% (mean +/- s.e. mean), and decreased marginally at an HCT of 24.2 +/- 0.1% (SS of 17.4 +/- 1.0% as compared to 20.2 +/- 1.6% at critical constriction (CC), P < 0.05). No increase in post-systolic shortening (PSS) occurred in the compromised area. Severe LAD dysfunction was observed in the LAD territory at an HCT of 14.9 +/- 0.1%, as systolic shortening decreased (11.8 +/- 1.1%, P < 0.01 vs CC) and PSS increased (31.2 +/- 3.4%, P < 0.01 vs CC). The effects of hemodilution on global cardiovascular and regional myocardial functions were unaffected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Influence of anesthesia on the threshold of pacing-induced ischemia.

Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/- 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow.

Animals↗

Pressure-length loop area: its components analyzed during graded myocardial ischemia.

The changes in total pressure-length loop area were compared with changes in effective shortening area, systolic lengthening area and postsystolic shortening area (defined with respect to end-diastolic and end-systolic lengths) of the pressure-length loop during myocardial ischemia in seven anesthetized dogs instrumented for measurement of left ventricular pressure and regional segmental wall motion (sonomicrometry) in the minor axis of the apical region of the left ventricle. Ischemia was induced by gradual tightening of a micrometer-controlled snare around the left anterior descending coronary artery, which supplied the apical myocardium. Data were obtained at normal flow, after critical constriction (loss of pulsatile coronary flow), mild ischemia (ischemia 1: onset of regional dysfunction, i.e., postsystolic shortening and mild hypokinesia) and moderate ischemia (ischemia 2: marked hypokinesia). At each stage, acute afterloading was performed by partially occluding the descending thoracic aorta. The pressure-length loops were analyzed in terms of four areas: total loop area, effective shortening area, postsystolic shortening area and systolic lengthening area. Total loop area decreased only when marked hypokinesia was present (176 +/- 18.3 mm Hg x mm at ischemia 2 versus 245.1 +/- 26.9 mm Hg x mm at ischemia 1, p less than 0.05). However, effective shortening area (98.2 +/- 0.8% of total loop area at baseline; 93.8 +/- 2.4% at critical constriction; 76.3 +/- 7.2% at ischemia 1; 51.9 +/- 12.2% at ischemia 2) and postsystolic shortening area (1.8 +/- 0.8% of total loop area at baseline; 5.2 +/- 1.9% at critical constriction; 14.3 +/- 3/4% at ischemia 1; 23.8 +/- 5.1% at ischemia 2) changed significantly with each progressive stage of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

End systolic pressure-length relations in halothane anaesthetised dogs: effects of regional ischaemia and inotropic agents.

STUDY OBJECTIVE: The aim was to investigate the effects of regional myocardial ischaemia, calcium, and verapamil on (a) the hysteresis and (b) slope and length axis intercept of the left ventricular end systolic pressure-length relationship. DESIGN: Segment length in myocardium supplied by the left anterior descending coronary artery was measured in anaesthetised dogs using sonomicrometry. Three levels of regional myocardial ischaemia were produced by stenosis and occlusion of the left anterior descending artery (ischaemia 1, ischaemia 2, and occlusion). A snare placed around the descending thoracic aorta was used to obtain temporary aortic occlusions. SUBJECTS: Seven open chested mongrel dogs were used, weight 17 kg (range 16-20). MEASUREMENTS AND MAIN RESULTS: After abrupt release of temporary aortic occlusions, end systolic lengths were greater than before the occlusion in the normal myocardium. This hysteresis was abolished by regional myocardial ischaemia. However, hysteresis was insensitive to calcium and verapamil. The length axis intercept of the end systolic pressure-length relationship was increased during ischaemia 2, during coronary occlusion, and after administration of verapamil; its slope was increased after coronary occlusion. CONCLUSIONS: (1) Viscoelastic properties of the myocardium make a major contribution to hysteresis of the end systolic pressure-length relationship; and (2) the length axis intercept of this relationship is not constant and its slope does not appear to be a sensitive indicator of regional myocardial contractility during regional ischaemia.

Anesthesia↗

Desensitization of myocardial beta-adrenergic receptors during cardiopulmonary bypass. Evidence for early uncoupling and late downregulation.

BACKGROUND: Cardiopulmonary bypass (CPB), a process routinely used during cardiac surgery, is a potent stimulant to the release of endogenous catecholamines. Hence, we tested the hypothesis that CPB results in myocardial beta-adrenergic receptor (beta AR) desensitization. METHODS AND RESULTS: We obtained canine transmyocardial left ventricular biopsies before, during (155 minutes), and after CPB (pre-CPB, CPB, and post-CPB, respectively) and determined beta AR density, proportion of beta 1AR to beta 2AR, and beta AR coupling capacity to adenylyl cyclase. Beta AR density was stable at 112 +/- 14 fmol/mg (pre-CPB) and 103 +/- 9 fmol/mg (CPB) but decreased post-CPB to 84 +/- 7 fmol/mg. The ratio of beta 1AR to beta 2AR (determined by two-site fit for [125I]-iodocyanopindolol competition binding with the beta 1AR selective antagonist ICI89.406) remained constant throughout (60 +/- 3: 40 +/- 3 pre-CPB, 55 +/- 3: 44 +/- 3 CPB, and 61 +/- 2: 39 +/- 2 post-CPB), revealing that both beta 1AR and beta 2AR subtypes were downregulated. A different pattern was noted in the functional properties of these receptors during CPB. Decreased maximal isoproterenol-stimulated adenylyl cyclase activity (252 +/- 14 to 216 +/- 12 pmol/30 min/mg), submaximal isoproterenol-stimulated adenylyl cyclase activity (183 +/- 10 to 157 +/- 11 pmol/30 min/mg), and zinterol-stimulated adenylyl cyclase activity (187 +/- 11 to 159 +/- 11 pmol/30 min/mg, a measure of beta 2AR subtype activation) were noted during CPB, at the time when weaning from CPB takes place. However, this desensitized pattern was found to be completely reversed by 30 minutes post-CPB, with adenylyl cyclase activities returning to pre-CPB levels or slightly higher. Control dogs that did not receive CPB showed no change in beta AR density or adenylyl cyclase activity. CONCLUSIONS: These data suggest that myocardial beta AR desensitization does occur during CPB in healthy, nonischemic canine myocardium and that this pattern is reversed 30 minutes after discontinuation of CPB. In addition, a slower process of beta AR downregulation persists after discontinuation of CPB. Because successful weaning from CPB is a critical process during myocardial surgery, these findings have potentially important implications in the management of such patients.

Adenylyl Cyclases↗

Effects of altered PaO2 and PaCO2 on left ventricular function and coronary hemodynamics in sheep.

The effects of acute changes in arterial carbon dioxide and oxygen tension, produced by altering the inspired gas mixtures while maintaining constant-volume intermittent positive pressure ventilation, on global function, regional left ventricular function, and coronary hemodynamics were studied in eight sheep during halothane anesthesia. Hypercapnia (Paco2, 73.5 +/- 2.3 mm Hg, mean +/- SD) increased heart rate, stroke volume, and cardiac output but decreased systolic shortening in the base of the left ventricle. Hypocapnia (PaO2, 24 +/- 1.5 mm Hg) decreased cardiac output and coronary flow below levels seen with hypercapnia but not below levels seen with normocapnia. Systolic shortening decreased in both apical and basal regions, and left ventricular relaxation was impaired as evidenced by a reduction of the nadir of LV dP/dt. Hypoxemia (PaO2, 39 +/- 1.5 mm Hg) elicited a hyperdynamic response of the circulation, increased coronary blood flow, and exhausted the coronary flow reserve. Neither changes in PaCO2 nor changes in PaO2 caused postsystolic shortening, although hypercapnia caused nonuniformity of contraction in the left ventricle. Thus, marked alterations in oxygen and carbon dioxide tensions do not cause left ventricular dysfunction, even though moderate hypoxia reduces the coronary flow reserve.

Anesthesia, Inhalation↗

Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs.

Cardiopulmonary bypass (CPB) with aortic cross-clamping represents a controlled period of global cardiac ischemia. We hypothesized that CPB (asanguineous prime), with aortic cross-clamping and repeated cardioplegia, alters myocardial function, which would be manifested as an exaggerated myocardial depression caused by halothane after CPB. In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0.0%-2.0%) were compared before and after CPB. A reduced mean arterial blood pressure (46.4 +/- 3.7 vs 85.8 +/- 5.9 mm Hg), associated with a marked hemodilution (hematocrit, 19% +/- 1% vs 41% +/- 2%), was observed after CPB. Cardiac output and systolic shortening were not significantly different after versus before CPB during fentanyl-midazolam anesthesia. Normalized to fentanyl-midazolam hemodynamics, halothane dose-response curves before and after CPB were identical for all variables except cardiac output, where halothane caused a slight but statistically significantly more pronounced decrease after CPB compared with before CPB. The effect of halothane on left ventricular function, therefore, is relatively unaffected by CPB with cardioplegia.

Animals↗

Effect of verapamil on canine left ventricular function in the presence of fentanyl when apical blood flow is critically limited.

Instruments were inserted to seven dogs under halothane anaesthesia, to measure global and regional left ventricular function. Anaesthesia was continued with fentanyl (100 micrograms kg-1 bolus, then 1.5 micrograms kg-1 min-1). Critical constriction was applied to the left anterior descending coronary artery. Control recordings were made, followed by bolus administration of verapamil 0.08, 0.16 and 0.32 mg kg-1, with recordings 10 min after each bolus. At the highest dose, verapamil decreased systemic arterial pressure, left ventricular dP/dt, stroke volume and systemic vascular resistance, and increased heart rate significantly. Coronary perfusion pressure decreased and, in the presence of critical constriction, coronary flow per beat decreased significantly. In the region with constriction, systolic shortening of myocardium decreased and post-systolic shortening increased significantly with addition of verapamil. The addition of a high dose of verapamil to fentanyl anaesthesia caused reduction in systolic function and development of early diastolic dysfunction in myocardium with critically limited blood supply.

Anesthesia, Intravenous↗

Regional differences in left ventricular wall motion in the anesthetized dog.

Data regarding left ventricular function suggest that the extent of shortening may differ between regions. This study was undertaken to determine the effects of negative inotropic drugs used during anesthesia on different areas of the left ventricle. Forty mongrel dogs were anesthetized and instrumented for measurement of global and regional function. Regional function in the short axis of the basal and apical territories of the left ventricle was assessed by subendocardial sonomicrometry. Three different interventions were performed: In the first group 67% N2O, replacing 67% N2, was added to opiate anesthesia; in the second group halothane was given by stepwise increases in inspired concentration to 2%; in the third group verapamil (60 micrograms.kg-1.h-1) was infused during isoflurane anesthesia. Apical and basal segmental shortening were compared. During baseline conditions and with agents in concentrations that caused minimal myocardial depression (67% N2O or 1.0% as opposed to 0.5% halothane) differences in systolic shortening between regions were statistically significant. Further myocardial depression affected the apex significantly more than the base: when substantial myocardial depression was induced by halothane (1.5 or 2%) or verapamil, differences in regional function were abolished. Thus, the apical region of the left ventricle is more dynamic and more sensitive to negative inotropic interventions than the basal region. This should be borne in mind when segmental myocardial function is evaluated.

Anesthesia, General↗

Effects of lignocaine and bupivacaine on regional myocardial function and coronary blood flow in anaesthetized dogs.

Empirical i.v. doses of lignocaine or bupivacaine of equal local anaesthetic potency were administered to halothane-anaesthetized dogs. Both local anaesthetics caused the expected depression of global haemodynamic function. Regional myocardial systolic shortening was depressed similarly by both agents. Regional myocardial dysfunction, seen as post-systolic shortening, occurred to a similar extent with both lignocaine and bupivacaine. Coronary blood flow and coronary perfusion pressure were significantly correlated during the administration of lignocaine; bupivacaine had erratic effects on coronary blood flow and no correlation between coronary blood flow and coronary perfusion pressure was seen. These results suggest that regional myocardial dysfunction occurs with both local anaesthetics and does not account for the apparent increased cardiotoxicity of bupivacaine. Bupivacaine did, however, cause wider individual variations compared with lignocaine with respect to coronary blood flow.

Anesthesia, General↗

Intravenous diltiazem worsens regional function in compromised myocardium.

The effect of intravenous diltiazem on regional myocardial function was assessed in a canine model of critical constriction of the left anterior descending coronary artery (LAD). Maintenance anesthesia with fentanyl (1.5 micrograms.kg-1.min-1), 60% inspired nitrous oxide, and 0.7% inspired halothane resulted in regional dysfunction, measured as postsystolic shortening (20.6 +/- 10.7%), which was significantly worsened after 0.1 mg/kg (48.7 +/- 12.5%, P less than 0.05) and after 0.2 mg/kg (68.8 +/- 11.7%, P less than 0.05) intravenous diltiazem. Systolic shortening in the compromised LAD territory was substantially depressed after 0.1 mg/kg diltiazem (8.2 +/- 0.6% to 5.3 +/- 1.3%, P less than 0.05) and was essentially abolished after 0.2 mg/kg diltiazem (8.2 +/- 0.6% to 0.7 +/- 2.3%, P less than 0.05). At the higher dose of diltiazem, cardiac output was substantially decreased (1.37 +/- 0.23 L/min to 0.88 +/- 0.30 L/min, P less than 0.05) and LV dP/dtmax significantly depressed (1090 +/- 90 mm Hg/sec to 744 +/- 80 mm Hg/sec, P less than 0.05). These results demonstrate significant depression of regional systolic shortening and substantial worsening of regional dysfunction in myocardium with a compromised blood supply, in association with significant depression of left ventricular performance, with intravenous diltiazem administration during anesthesia.

Anesthesia, Inhalation↗