Biomedical subjects

R B Hinton

Publications and source records attributed to R B Hinton.

10 recordsLinked to original sources

PubMed1997

Potassium channel opener-augmented cardioplegia: protection of myocyte contractility with chronic left ventricular dysfunction.

BACKGROUND: An increased number of patients with preexisting left ventricular (LV) dysfunction and congestive heart failure (CHF) are undergoing cardiac surgery with a higher risk for decreased LV contractility after hyperkalemic cardioplegic arrest. Activation of adenosine triphosphate-sensitive potassium channels by potassium channel openers (PCO) within the myocyte appears to confer a protective effect in the setting of ischemia. Accordingly, the present study was designed to determine whether PCO supplementation during hyperkalemic cardioplegic arrest would provide protective effects on myocyte contractile function, particularly in the setting of CHF. METHODS AND RESULTS: LV myocytes were isolated from control pigs (n=7) and pigs with CHF (rapid pacing, 240 beats per minute; n=7) and then assigned to the following treatment groups: normothermia (cell culture media, 2 hours, 37 degrees C); cardioplegia (24 mEq/L K+, 2 hours, 4 degrees C; then 10 minutes of reperfusion); or PCO/cardioplegia (cardioplegia supplemented with 100 micromol/L of the PCO aprikalim). Myocyte velocity of shortening was reduced in both control (66+/-2 versus 33+/-1 microm/s) and CHFmyocytes (32+/-1 versus 22+/-1 microm/s) after hyperkalemic cardioplegic arrest (P<.05). Contractility after PCO cardioplegia was similar to normothermic values in control (57+/-2 microm/s) and CHF (33+/-1 microm/s) myocytes (P<.05). Intracellular free Ca2+ increased from normothermia during hyperkalemic cardioplegia in control (81+/-4 to 145+/-7 nmol/L) and CHF (262+/-30 to 823+/-55 nmol/L) myocytes (P<.05). PCO cardioplegia attenuated the intracellular increase in free Ca2+ during the cardioplegic interval in control (110+/-6 nmol/L) and CHF (383+22 nmol/L) myocytes (P<.05). CONCLUSIONS: PCO-augmented cardioplegic arrest preserved myocyte contractility and reduced the intracellular free Ca2+ release, which therefore may be of particular benefit in the setting of preexisting LV dysfunction.

Animals↗

PubMed1997

Preservation of myocyte contractile function after hyperthermic cardioplegic arrest by activation of ATP-sensitive potassium channels.

BACKGROUND: Left ventricular (LV) dysfunction can occur after hyperkalemic cardioplegic arrest and subsequent reperfusion and rewarming. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels within the myocyte sarcolemma has been shown to be cardioprotective for myocardial reperfusion injury and ischemia and may play a contributory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and activation of KATP channels by a potassium channel opener (PCO) would attenuate alterations in ionic homeostasis and improve myocyte contractile function. METHODS AND RESULTS: Porcine LV myocytes were isolated and randomly assigned to the following treatment groups: normothermic control, incubation in cell culture media for 2 hours at 37 degrees C (n=60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incubation in cardioplegic solution containing 100 micromol/L of the PCO aprikalim (n=60). Hyperkalemic cardioplegia and rewarming caused a significant reduction in myocyte velocity of shortening compared with normothermic control values (33+/-2 versus 66+/-2 microm/s, P<.05). Cardioplegic arrest with PCO supplementation significantly improved indices of myocyte contractile function when compared with hyperkalemic cardioplegia (58+/-4 microm/s, P<.05). Myocyte intracellular calcium increased during hyperkalemic cardioplegic arrest compared with baseline values (147+/-2 versus 85+/-2 nmol/L, P<.05). The increase in intracellular calcium was significantly reduced in myocytes exposed to the PCO-supplemented cardioplegic solution (109+/-4 nmol/L, P<.05). CONCLUSIONS: Cardioplegic arrest with simultaneous activation of KATP channels preserves myocyte contractile processes and attenuates the accumulation of intracellular calcium. These findings suggest that changes in intracellular calcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for preservation of myocyte contractile function during cardioplegic arrest.

Animals↗

PubMed1997

Left ventricular regional myocyte contractility in normal and heart failure states.

Fundamental determinants of left ventricular (LV) pump performance are preload, afterload and myocyte contractility. Regional variability in LV end systolic wall stress, an important index of LV afterload, has been well defined in both control and congestive heart failure (CHF) states. The goal of this study was to examine end systolic wall stress and myocyte contractile function in three circumferential regions of the LV in both control and CHF states. Accordingly, LV end systolic wall stress and myocyte velocity of shortening were measured from the basal, mid and apical regions in control pigs (n=5) and following the induction of pacing-induced CHF (3 weeks, 240 beats/min, n=5). LV mid wall, circumferential, end systolic wall stress decreased from base to apex in both control (35+/-7 v 16+/-4 g/cm2, P<0.05) and CHF (155+/-23 v 92+/-24 g/cm2, P<0.05) states. In the CHF group, LV end systolic wall stress was elevated by 300% compared to control values in all regions. LV myocyte velocity of shortening was equivalent in the basal and mid regions of control myocytes (52+/-2 v 57+/-2 m/s), and was higher in the apical region (63+/-3 microm/s, P<0.05). In the CHF group, LV myocyte velocity of shortening was reduced by 45% compared to controls with no regional variation. beta-adrenergic stimulation increased myocyte velocity in both the control and CHF groups, however, regional variation was observed only in the CHF group. These unique results demonstrated that minimal regional variations in myocyte contractile function exist in both control and congestive heart failure states, and does not necessarily parallel patterns of regional LV end systolic wall stress.

Animals↗

PubMed1997

Impact of embolization during coronary artery bypass grafting on outcome and length of stay.

BACKGROUND: Transcranial Doppler ultrasonography detects emboli in most patients during coronary artery bypass grafting. However, the significance of these emboli has not yet been established. METHODS: We monitored 82 patients during coronary artery bypass grafting with this technique and related the numbers of emboli to the outcomes and length of hospital stay. RESULTS: We detected cerebral emboli in all patients. Patients with stroke (n = 4; 4.9%) had a mean of 449 emboli, as compared with 169 emboli in patients without stroke (n = 78) (p = 0.005). Patients with major cardiac complications (n = 7) had a mean of 392 emboli, as compared with 163 in patients without such complications (n = 75) (p = 0.003). The mean hospital stay of survivors was 8.6 days in patients with fewer than 100 emboli (n = 40), 13.5 days in patients with 101 to 300 emboli (n = 23), 16.3 days in those with 301 to 500 emboli (n = 16), and 55.8 days in patients with more than 500 emboli (n = 6) (p = 0.0007). This relation was unchanged when patients with complications were excluded. The correlation between embolization and outcome was independent of the extent of aortic atheroma or age. CONCLUSIONS: Emboli detected during coronary artery bypass grafting are significantly related to major cardiac and neurologic complications and affect length of stay in all patients, even in the absence of such specific complications.

Adult↗

PubMed1997

Aortic atheroma is related to outcome but not numbers of emboli during coronary bypass.

BACKGROUND: The relation between aortic atheroma severity and stroke after coronary artery bypass grafting is established. The relation between atheroma severity and other outcome measures or numbers of emboli has not been determined. METHODS: Using transesophageal echocardiography, we determined the severity of atheroma in the ascending, arch, and descending aortic segments in 84 patients undergoing operations. Seventy patients were monitored using transcranial Doppler ultrasonography. RESULTS: The incidence of stroke was 33.3% among 9 patients with mobile plaque of the arch and 2.7% among 74 patients with nonmobile plaque (p = 0.011). Cardiac complications were not significantly related to atheroma severity in any aortic segment. Length of stay was significantly related to atheroma severity in the aortic arch (p = 0.025) and descending segment (p = 0.024). The presence of severe atheroma in both the arch and descending segments was associated with significantly longer hospital stays as compared with patients with severe atheroma in neither segment (p = 0.05). Numbers of emboli were greater in patients with severe atheroma at clamp placement, although the differences did not achieve statistical significance. CONCLUSIONS: Aortic atheroma severity is related to stroke and to the duration of hospitalization after coronary artery bypass grafting. The lack of correlation between numbers of emboli and atheroma severity suggests that m any emboli may be nonatheromatous in nature.

Adult↗

PubMed1996

Direct effects of oxygenated crystalloid or blood cardioplegia on isolated myocyte contractile function.

UNLABELLED: The majority of myocardial protective techniques performed in the United States incorporate hypothermic, hyperkalemic blood or crystalloid cardioplegia. Oxygenated blood cardioplegia has not been compared with oxygenated crystalloid cardioplegia in an isolated myocyte model of hypothermic, hyperkalemic cardioplegic arrest in which direct measurements of contractile function and myocyte swelling can be made. Accordingly, isolated myocyte contractile function and myocyte profile surface area were examined after hypothermic arrest with oxygenated crystalloid or blood cardioplegia. METHODS: Isolated left ventricular pig myocytes were randomly assigned to undergo cardioplegic arrest for 2 hours at 4 degrees C. Either oxygenated crystalloid or blood cardioplegia was used. After 2 hours, myocytes were reperfused with standard cell medium at 37 degrees C and contractile function was examined. A control group of myocytes was maintained in cell medium at 37 degrees C for 2 hours. Myocyte velocity of shortening (micrometers per second) was examined at baseline and after beta-adrenergic stimulation (isoproterenol, 25 nmol/L). Velocity of shortening declined equally from baseline control values (65 +/- 2 micron n/sec) in the groups subjected to oxygenated crystalloid cardioplegia and blood cardioplegia (37 +/- 2 micron n/sec and 42 +/- 1 micron n/sec, respectively; p < 0.05). RESULTS: Although beta-adrenergic stimulation caused a significant increase in velocity of shortening in all myocyte groups, the increase was less pronounced in myocytes subjected to crystalloid cardioplegia (157 +/- 6 micron n/sec) and blood cardioplegia (159 +/- 6 micron n/sec) than in normothermic control myocytes (205 +/- microm/sec; p < 0.05). Myocyte profile surface area, an index of cell volume, was measured in all myocyte groups. Myocyte surface area increased equally after cardioplegic arrest and rewarming in both cardioplegia groups (crystalloid 4119 +/- 53 micron2; blood 3924 +/- 48 micron2); surface areas in both cardioplegia groups were significantly greater than in the normothermic control group (3158 +/- 39 micron2, p < 0.05). CONCLUSION: Equivalent effects of oxygenated crystalloid and blood cardioplegia were observed with respect to myocyte contractile function, inotropic responsiveness, and intracellular volume regulatory processes.

Animals↗

PubMed1996

Developmental differences in myocyte contractile response after cardioplegic arrest.

Although developmental differences in left ventricular function after cardioplegic arrest and rewarming have been postulated, whether differences exist at the level of the myocyte remains unexplored. This project tested the hypothesis that there is a differential effect of hypothermic hyperkalemic cardioplegic arrest with subsequent rewarming on contractile function of immature compared with adult ventricular myocytes. Myocytes were isolated from the left ventricular free wall of five immature and five adult rabbits and incubated for 2 hours in hyperkalemic modified Ringer's solution at 4 degrees C (cardioplegia) or for 2 hours in cell culture medium at 37 degrees C (normothermia). Myocytes were resuspended ("rewarmed") in 37 degrees C cell culture medium after the incubation protocol. Normothermic baseline contractile performance was lower in immature, compared with adult, myocytes. Specifically, myocyte shortening velocity was 62 +/- 4 microm/sec in immature and 112 +/-6 microm/sec in adult myocytes (p < 0.01). After cardioplegia and rewarming, immature myocyte contractile function was unchanged, whereas adult myocyte contractile function was significantly diminished. For example, myocyte shortening velocity was 65 +/- 4 microm/sec in immature and 58 +/- 3 microm/sec in adult myocytes (p < 0.01 versus normothermic). Myocyte surface area, which reflects myocyte volume, was increased after cardioplegia and rewarming in adults (3582 +/- 55 versus 3316 +/- 46 microm2, p < 0.01), but remained unchanged in immature myocytes (2212 +/- 27 versus 2285 +/- 28 microm2, P = not significant). These unique findings demonstrate a preservation of myocyte contractile function and volume regulation in immature myocytes after cardioplegic arrest and rewarming. Thus this study directly demonstrates that developmental differences exist in myocyte responses to hypothermic hyperkalemic cardioplegic arrest with subsequent rewarming.

Animals↗

PubMed1996

Preservation of myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest with 2, 3-butanedione monoxime.

One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37 degrees C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because beta-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3 butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although beta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest.

Animals↗

PubMed1996

Horner's syndrome after coronary artery bypass surgery.

We established the frequency of Horner's syndrome (HS) in 248 elective patients after coronary artery bypass surgery. Patients were evaluated neurologically pre- and post-operatively and 6 months after surgery. Nineteen patients (7.7%) developed unilateral HS postoperatively, 12 involving the left eye. The finding persisted in 10 patients (4%) at 6 months. When assessed 2 to 6 days, or 6 months, postoperatively, HS tended to be isolated and not associated with C8/T1 plexopathy. Among nondiabetic subjects, hypertensive patients had a higher frequency of HS than normotensive patients (10.6% versus 2.9%, p = 0.05). Among normotensive subjects, diabetic patients had a higher frequency than nondiabetic patients (15% versus 2.9%, p = 0.08). There was no association between HS, age, sex, internal mammary artery grafting, or length of cardiopulmonary bypass time. In summary, HS is a common and sometimes persistent complication of coronary artery bypass surgery. Hypertensive, and possibly diabetic, patients appear to be at greatest risk for developing HS.

Adult↗

PubMed1994

Cerebral emboli detected during bypass surgery are associated with clamp removal.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography detects embolic signals during coronary artery bypass surgery. The relationship between embolization and specific events of bypass surgery is unclear. METHODS: With this technique, 20 patients undergoing bypass surgery were continuously monitored from inception to discontinuation of bypass. RESULTS: Embolic signals were detected in all patients. Of all embolic signals, 34% were detected as aortic cross-clamps were removed, and another 24% as aortic partial occlusion clamps were removed. Only 5% were detected at inception of bypass. Rates for embolization were 15.15 embolic signals per minute at cross-clamp removal, 10.9 embolic signals per minute at partial occlusion clamp removal, and fewer than 3 embolic signals per minute at other times. Correlation was found between the number of emboli, severity of aortic atheromatosis, and neurocognitive deterioration. CONCLUSIONS: The majority of emboli detected during coronary artery bypass grafting are associated with the release of clamps. Clamp manipulation may lead to release of aortic atheromatous debris. These emboli may be relevant to neurocognitive outcome.

Aged↗