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Biomedical subjects

M Amrani

Publications and source records attributed to M Amrani.

At least 55 records · Page 3Linked to original sources
PubMed1999

Coronary vasoconstriction to endothelin-1 increases with age before and after ischaemia and reperfusion.

OBJECTIVE: Ageing is known to be associated with changes within the heart. We investigated whether the coronary response to endothelin-1 (ET) and sarafotoxin S6c (S6c) is altered with increasing age, before and after cardioplegic arrest. METHODS: Using an isolated rat heart model, increasing concentrations of ET and S6c were administered to rats of different ages (group I = one month; group II = five months; group III = 21 months). An identical series of experiments was performed following the addition of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) to the Krebs perfusion fluid. In a third series of experiments, increasing doses of ET-1 were added to hearts following 4 h of cardioplegic arrest at 4 degrees C. RESULTS: Coronary flows are expressed as a percentage of initial coronary flow +/- SEM. There was a greater decrease in coronary flow in the older rats for all doses of ET-1. ET-1 (10(-9) M) reduced coronary flows to 72.8 +/- 3.7, 53.2 +/- 6.7 and 56.5 +/- 10.7% for groups I-III respectively (P = 0.01 I vs. II; P = 0.1 I vs. III). A similar response to ET-1 was seen in hearts perfused with indomethacin and L-NAME when compared to those perfused without (P = NS). Perfusion with ET-1 (10(-9) M) following 4 h of cardioplegic arrest reduced coronary flows to 40.5 +/- 4.9, 26.8 +/- 4.8 and 24.1 +/- 3.9%, respectively (P = 0.08 I vs. II; P = 0.03 I vs. III). Perfusion with S6c (10(-10) M) produced coronary flows of 93.3 +/- 5.5, 77.0 +/- 3.5 and 73.9 +/- 3.9% for groups I-III, respectively (P = 0.03 I vs. II; P = 0.01 I vs. III). Perfusion with S6c (10(-9) M) in the presence of L-NAME and indomethacin reduced coronary flows to 85.7 +/- 3.0, 81.6 +/- 2.2 and 74.6 +/- 3.6% (P = NS I vs. II; P = 0.03 I vs. III). CONCLUSIONS: The coronary vasoconstrictor response to ET-1 and S6c increases with age. The increased vasoconstriction in response to ET-1 is independent of the decrease in NO release seen with ageing.

Aging↗
PubMed1999

Heat stress proteins and myocardial protection: experimental model or potential clinical tool?

Heat stress proteins (hsp) are induced by a variety of stimuli including elevated temperature, ischaemia, hypoxia, pressure overload and some chemicals. They help to maintain the metabolic and structural integrity of the cell, as a protective response to external stresses. They are known to protect the myocardium from the damaging effects of ischaemia and reperfusion. The heat stress response results in accumulation of heat stress proteins. The beneficial effects associated with their expression include improved endothelial and mechanical recovery of the ischaemic heart. In addition, preservation of high energy phosphates and reduction in infarct size. It has also been shown that critical amounts of hsp70 are necessary to ensure protection of the myocardium. However, questions remain regarding the biochemical mechanisms underlying this protective effect. Alterations in the cell metabolism and chaperone function of cells expressing heat shock proteins, are thought to be responsible. Despite the obvious clinical benefits related to the heat stress response in a clinical setting, the application of this phenomena remains limited. Heat, both quantitatively and qualitatively is one of the best inducers of heat stress proteins. However, the effects of heat stress are nonspecific and intracellular damage is a common occurrence. The search for alternative stimuli, particularly within the fields of pharmacotherapy or genetic manipulation may offer more viable options, if the heat stress response is take its place as an established strategy for myocardial protection.

Animals↗
PubMed1999

Characterisation of constrictor endothelin receptors in the human internal thoracic artery and saphenous vein.

We studied the endothelin receptors mediating contraction in the human saphenous vein (SV) and internal thoracic artery (ITA). In the SV, the ET(A)-receptor antagonist BQ123 (1 microM) did not significantly shift the ET-1 concentration-response curve but did cause a parallel shift in the ITA. In the SV, the ET(A)-receptor agonist sarafotoxin 6b (S6b) produced a monophasic concentration-response curve that was antagonised biphasically by BQ123 (0.1-1 microM). In the ITA, S6b was an ineffective agonist with contractions seen only at 3 x 10(-9) M upward. The ET(B)-receptor agonist sarafotoxin 6c (S6c) caused constrictions in only 74% of SV rings and 42% of ITA rings. In the tissues that did respond, S6c caused a monophasic concentration-response curve with a lower maximal response than ET-1. The ET(B) antagonist BQ788 did not antagonise the responses to ET-1 in either the SV or the ITA but did antagonise the responses to S6c in the SV. The results from this study suggest that mainly ET(A) receptors mediate the contractile responses in the human SV and ITA. There is also evidence for an ET(B)-mediated response, although the contractions were much smaller than those elicited by ET-1. We also conclude that the ET(A) receptors mediating responses in these human vessels are atypical because of the different effects of BQ123 on the two vessels.

Adult↗
PubMed1999

[Squamous cell carcinoma in an augmentation of the ilial bladder for tuberculosis].

The development of cancer on the ileal graft after augmentation ileocystoplasty benign bladder disease is a little known complication. The authors report a case of squamous cell carcinoma in the ileal bladder occurring 31 years after augmentation ileocystoplasty for tuberculous bladder, in a 60-year-old patient. The ileal bladder was resected and a new augmentation ileocystoplasty was performed. The postoperative course was uneventful. Histological examination of the operative specimen showed infiltration of all of the intestinal wall. The patient died one year after, in a context of peritoneal carcinomatosis.

Carcinoma, Squamous Cell↗
PubMed1999

Effects of heat stress on metabolism of high-energy phosphates. Comparison of normothermic and hypothermic ischemia.

BACKGROUND: Alterations in metabolic pathways may contribute to the cardioprotective effects of heat stress (HS). We investigated the effects of HS on ATP and phosphocreatine (PCr) levels in the ischemic rat myocardium, after both normothermic and hypothermic ischemia. METHODS: Two protocols were used: (1) normothermic ischemia (20 min at 37 degrees C) with no myocardial protection (n=6 HS; n=6 control); (2) hypothermic ischemia (4 hrs at 4 degrees C) after cardioplegic arrest (n=6 HS; n=6 control). ATP and PCr levels in the heart were measured using 31P nuclear magnetic resonance spectroscopy. RESULTS: At the end of normothermic ischemia, ATP levels were better maintained in HS hearts (C vs HS: 4.51+/-0.66 vs 7.81+/-1.06 micromol/g dry wt+/-SEM, p=0.04). A trend for higher ATP content in HS hearts was observed after 40 min of reperfusion (C vs HS: 11.7+/-1.5 vs 16.9+/-2.0 micromol/g dry wt+/-SEM, p=0.09). PCr content was also higher at the end of 40 minutes of reperfusion in HS hearts (C vs HS: 46.4+/-2.9 vs 56.9+/-3.0 micromol/g dry wt+/-SEM, p=0.03). After prolonged hypothermic ischemia under cardioplegic arrest, heat stress again led to better preservation of ATP levels at the end of ischemia (C vs HS: 5.71+/-0.88 vs 9.23+/-1.38 micromol/g dry wt+/-SEM, p=0.05) and after 40 minutes of reperfusion (C vs HS: 16.8+/-1.4 vs 24.6+/-2.8 micromol/g dry wt+/-SEM, p=0.03). PCr levels were also better maintained at the end of ischemia (C vs HS: 4.87+/-0.77 vs 12.4+/-3.0 micromol/g dry wt+/-SEM, p=0.03) and after 40 minutes of reperfusion in HS hearts (C vs HS: 55.1+/-7.0.vs 79.8+/-7.3 micromol/g dry wt+/-SEM, p=0.03). CONCLUSIONS: Heat stress induces changes in the energy profile of the heart which results in better preservation of ATP and phosphocreatine levels. These changes could be observed after brief normothermic ischemia and also after prolonged hypothermic ischemia under cardioplegic arrest, mimicking conditions of preservation for cardiac transplantation.

Adenosine Triphosphate↗
PubMed1998

Role of endogenous endothelin in the regulation of basal coronary tone in the rat.

1. Coronary vascular tone is a vital factor that regulates the delivery of oxygen to cardiac muscle. We tested the hypothesis that basal coronary tone may depend on the release of an endogenous vasoconstrictor peptide, endothelin (ET). 2. Using an isolated, Krebs solution-perfused rat heart we measured the changes in coronary flow following the administration over a 30 min period of the ET antagonists Ro61-0612 (mixed ETA/ETB), PD155080 (ETA) and BQ788 (ETB). 3. In a second series of experiments, hearts were randomly assigned to perfusion with plain Krebs solution, or with Krebs solution to which L-NAME and/or indomethacin had been added. The effect on coronary flow following the addition of Ro61-0612 was then measured. 4. Perfusion with Ro61-0612 (10-4 M) alone increased coronary flow by 57.8 % vs. control (P = 0.00001). PD155080 (10-4 M) increased coronary flow by 28.9 % (P = 0.009), whereas BQ788 had no effect on coronary flow. 5. In the second series of experiments, Ro61-0612 increased coronary flow by 6.6 +/- 0.8 ml min-1 in hearts perfused with plain Krebs solution, by 3.8 +/- 0.8 ml min-1 in hearts to which both L-NAME and indomethacin had been added, by 3.3 +/- 0.7 ml min-1 in hearts to which L-NAME had been added, and by 6. 9 +/- 0.5 ml min-1 in hearts to which indomethacin had been added to the Krebs buffer. 6. In hearts perfused with Krebs solution alone, nitric oxide (NO) release into the coronary sinus increased from 219. 8 to 544.9 pmol min-1 g-1 following the addition of Ro61-0612 (P = 0. 06). There was no detectable release of NO from hearts perfused with L-NAME alone or in combination with indomethacin either before or after the addition of Ro61-0612. 7. We conclude that endogenous ET plays a role in coronary tone mediated via ETA receptors. This vasodilatation is partially due to an increase in endogenous NO release. However, a significant vasodilatation is still seen following the inhibition of NO synthesis. We propose that basal coronary tone depends on a balance between the endogenous release of vasodilators such as NO and vasoconstrictors such as ET.

Animals↗
PubMed1998

Relative induction of heat shock protein in coronary endothelial cells and cardiomyocytes: implications for myocardial protection.

OBJECTIVES: Induction of the 70 kd heat shock protein in the heart is known to exert a protective effect against postischemic mechanical and endothelial dysfunction. However, the exact site of induction and the mechanisms involved remain unknown. The aim of this study was to investigate the relative capacity of endothelial and myocardial cells to express the 70 kd heat shock protein in response to heat stress, as well as their significance. METHODS: (1) Postischemic recovery of cardiac mechanical and endothelial function was studied in isolated rat hearts with and without endothelial denudation with saponin. (2) Semiquantitative determination of induction of 70 kd heat shock protein by Western immunoblotting was performed in the whole cardiac homogenate, in isolated cardiac myocytes, and in coronary endothelial cells. (3) Immunocytochemistry was used to visualize the distribution of induction of 70 kd heat shock protein in both cell types. RESULTS: Postischemic recovery (percent preischemic value +/- standard error of the mean) of cardiac output in hearts from heat-stressed animals was significantly improved (66.7 +/- 6.9 vs 44.5 +/- 4.5 in the control group, p < 0.01). In heat-stressed hearts treated with saponin no improvement in the recovery of cardiac output was noted (44.7 +/- 6.9 in heat-stressed hearts vs 38.0 +/- 4.0 in heat-stressed, saponin-treated hearts, p = not significant). Endothelial function (as assessed by the vasodilatory response to the endothelium-dependent vasodilator 5-hydroxytryptamine) improved from 31.0 +/- 5.2 in the control group to 65.8 +/- 7.1 in heat-stressed hearts (p < 0.02 vs control) and dropped to -1.9 +/- 3.8 in heat-stressed hearts treated with saponin. Immunocytochemistry showed that only sections of hearts from heat-treated rats showed a strong specific reaction with heat shock protein antibody. The positive staining was seen in endothelial cells. Induction of 70 kd heat shock protein content in the whole cardiac homogenate from heat-stressed rats as measured by Western immunoblotting was 5.2 +/- 1.9 (vs 0.0 in non-heat-stressed rats, p < 0.0001) and dropped to 0.0 in heat-stressed hearts treated with saponin. The tentative amount of 70 kd heat shock protein was 18.1 +/- 7.8 in isolated endothelial cells from heat-stressed hearts and 2.3 +/- 2.3 in isolated cardiac myocytes (p < 0.01 vs endothelial cells). CONCLUSIONS: Coronary endothelial cells are the main site of induction of 70 kd heat shock protein in the heart and appear to contribute to the protective effects of heat stress on the recovery of mechanical and endothelial function.

Animals↗
PubMed1998

Long-term survival after aortic valve replacement for native active infective endocarditis.

BACKGROUND: The objective of this study was to analyse the impact of acute surgery for native aortic valve endocarditis and its influence on the long-term prognosis after surgery. METHODS: A total of 161 patients underwent aortic valve replacement for native active aortic valve endocarditis (NAAVE) during a 29-year period, from 1967 to 1995 (age range: 10 to 72 years; mean 48 +/- 12). The main indication for surgery was progressive congestive heart failure (76%). Other indications were untreatable sepsis (27%), peripheral or central emboli (12%) and, from 1978, echocardiographic evidence of friable, pedunculated vegetations (3%). Streptococcal and staphylococcal infections predominated. Concomitant procedures were performed in 27% of the patients, including mitral and tricuspid valve surgery and coronary bypass procedures. RESULTS: Operative mortality was 8% in the majority of cases caused by heart failure or multi-organ failure. Multivariate logistic regression analysis identified NYHA class IV to be an independent predictor for postoperative death. Long-term survival for discharged patients was 75% at 10 years and 58% at 15 years, with a mortality rate of 3.6%/patient/year. Cox regression analysis identified the year of operation, trivalvular endocarditis and staphylococcal infection as independent predictors of survival. At 10 and 15 years after aortic valve replacement, 91% and 84% of the patients, respectively, were free of recurrent endocarditis. The presence of an abscess cavity at first operation was found to be predictive of recurrent endocarditis. CONCLUSIONS: Valve replacement for NAAVE offers a good chance for a cure and satisfactory long-term survival. Improvements in pre- and per-operative management of the very ill patient, and the use of allograft valves are likely to further improve long-term results. Finally, the presence of staphylococcal endocarditis requires long-term postoperative antibiotic therapy.

Adolescent↗
PubMed1998

Influence of ageing on functional recovery and guanine nucleotide levels of the heart following cold cardioplegic arrest.

OBJECTIVE: The effect of age on metabolism and mechanical recovery of the heart after cardioplegic arrest is important, but remains a relatively unexplored subject. In this study, functional recovery and nucleotide levels were compared in the heart at different ages subjected to prolonged hypothermic cardioplegic arrest. METHODS: Three different age groups of rats: 1 (A); 4 (B); and 16 months (C) were perfused in working mode and subjected to cardioplegic arrest (St. Thomas' No. 1) and ischemia for 4 h at 4 degrees C, followed by reperfusion for 35 min. Cardiac function (cardiac output and aortic pressure) was recorded before and after ischemia. Another series of hearts in all three age groups underwent 5 min of normoxic perfusion to obtain pre-ischemic baseline metabolite concentrations. Hearts were freeze-clamped at the end of each experiment and used for determination of nucleotide and creatine metabolites by HPLC. RESULTS: The post-ischemic recovery (% of the pre-ischemic value) of the cardiac power was 48.9 +/- 7.8% for group A, which was significantly higher than the functional recovery of group B (24.1 +/- 3.5%) or C (21.4 +/- 4.7%, P < 0.05, respectively). There was no difference in ATP or the total adenine nucleotide or creatine metabolite concentrations between the three age groups. In contrast, both GTP and the total guanine nucleotide concentration was highest in A (P < 0.05). Total guanylate pool was 1.52 +/- 0.10 1 micromol/g dry wt. in A, as compared to B (1.05 +/- 0.04) or C (1.12 +/- 0.04). NAD was significantly higher in B (4.1 +/- 0.1. P < 0.05), when compared to A (3.6 +/- 0.1) and C (3.8 +/- 0.1). CONCLUSION: Best post-ischemic functional recovery after cardioplegic arrest was observed in the 1-month-old hearts (A) and was associated with highest guanine nucleotide concentration; preservation of guanine nucleotide pool in the youngest hearts may be an important mechanism for improved cardioprotection due to the important role of GTP in signalling pathways.

Aging↗
PubMed1998

Influence of heat stress on myocardial metabolism and functional recovery after cardioplegic arrest: a 31P N.M.R study.

OBJECTIVE: Heat stress and induction of heat shock proteins confer protection against myocardial ischemia-reperfusion injury; however the precise mechanisms of this effect remain unknown. We investigated the influence of heat stress on metabolic and functional recovery after cardioplegic arrest, in a protocol mimicking clinical donor heart preservation. METHODS: Langendorff perfused rat hearts in control group (C, n = 6) and heat stressed (24 h prior to experiment) group (HS, n = 6) were subjected to 4 h of ischemia at 4 degrees C following cardioplegic arrest (St. Thomas' No. 1). 31P nuclear magnetic resonance spectroscopy was used to follow changes in ATP, phosphocreatine and inorganic phosphate concentrations during the pre-ischemic, ischemic and reperfusion periods. Myocardial adenine nucleotide levels in hearts at the end of experiments and purine catabolite release in coronary effluent during reperfusion, were evaluated using high performance liquid chromatography. Mechanical function in the pre-ischemic and reperfusion periods was evaluated using an intraventricular balloon. Western immunoblotting was used to quantitate HSP70 expression. RESULTS: Although baseline concentrations of ATP and phosphocreatine were similar in C and HS groups, the rate of high-energy phosphate depletion was attenuated during the early phase of ischemia in HS groups. On reperfusion, recovery of ATP was 10-20% greater in HS versus C groups; phosphocreatine levels also recovered better in the HS group, transiently reaching levels 40% higher in HS versus C groups. The concentrations of adenine nucleotides in hearts were significantly higher in the HS versus C groups. These changes were associated with an attenuation of total purine catabolite release in the coronary effluent in HS versus C groups. A significant improvement in relative recovery of developed pressure was shown in HS versus C groups in the post-ischemic periods. CONCLUSIONS: Heat stress causes beneficial changes in high-energy phosphate metabolism in the rat heart subjected to cardioplegic arrest and ischemia. Improved mechanical recovery in HS versus C groups was associated with a decreased rate of high-energy phosphate depletion and increased recovery of ATP and phosphocreatine levels during reperfusion. Changes in energy metabolism may play a role in the mechanism of cardioprotection by heat stress during prolonged hypothermic cardiac arrest. rights reserved.

Adenosine Triphosphate↗
PubMed1998

Vascular biology of the radial artery.

In recent years, the use of the radial artery as a coronary artery bypass graft has enjoyed a revival. This follows the initial disappointing results with the use of this blood vessel experienced by Carpentier and colleagues in the early 1970s. The improvement in the performance of the radial artery is believed to be caused by improved harvesting techniques and the use of vasodilator drugs. However, compared with the other blood vessels used as bypass grafts, little is known about the vascular biology of this artery. The reactivity of the smooth muscle and protection offered by the vascular endothelium are known to be important factors that may determine the suitability of different arteries and veins to act as bypass conduits. The aim of this review is to examine how the properties of the vessel wall may contribute to the performance of the radial artery when used as a coronary artery bypass graft.

Coronary Artery Bypass↗
PubMed1997

The effect of L-arginine on myocardial recovery after cardioplegic arrest and ischemia under moderate and deep hypothermia.

BACKGROUND: Depletion of L-arginine (L-arg), the substrate for nitric oxide (NO) synthesis, could be one of the mechanisms responsible for the reduced production of NO and decreased coronary flow (CF) during reperfusion. This, in turn, may adversely affect mechanical function. We aimed to study the benefits of exogenous administration of L-arg under conditions that mimick preservation of the heart for transplantation and routine cardiac surgery. METHODS AND RESULTS: Isolated working rat hearts perfused with oxygenated Krebs-Henseleit buffer were subjected to one of the two experimental protocols: (1) cardioplegic arrest with St Thomas' No 1 cardioplegic solution and 240 minutes of deep hypothermic (4 degrees C) ischemia, and (2) cardioplegic arrest with St Thomas' No 1 cardioplegic solution and 60 minutes of moderate hypothermic (20 degrees C) ischemia. In each protocol, hearts were divided into four groups (1 to 4 for protocol A and A through D for protocol B; n=6 in each group). In groups 1 and A (controls), hearts were arrested with the St Thomas' No 1 and were reperfused with standard Krebs-Henseleit buffer. In groups 2 and B, L-arg was added to cardioplegic fluid; in groups 3 and C, L-arg was added to reperfusate; and in groups 4 and D, L-arg was added to both cardioplegic fluid and reperfusate. Cardiac output, dP/dt, CF, and NO concentrations in the coronary effluent were evaluated in all groups before and after ischemia. After 4 degrees C ischemia (protocol A), the postischemic recovery of dP/dt for the control hearts in group 1 was 51.0+/-3.4%, which increased significantly to 73.3+/-2.7% and 70.1+/-4.4% in groups 3 and 4, respectively. In group 2, recovery of dP/dt was similar to the control group's and was 56.5+/-4.5%. Increased postischemic cardiac output and CF and increased production of NO correlated with improved functional recovery. After 20 degrees C ischemia (protocol B), the postischemic recovery of dP/dt was 47.2+/-3.5% in control group A and significantly increased to 79.2+/-2.6% in group B, to 82.0+/-3.5 in group C, and to 83.9+/-3.3 in group D. Increased postischemic CF and increased production of NO were closely related to improvement in mechanical function. CONCLUSIONS: Exogenous L-arg considerably improves the postischemic recovery of cardiac mechanical function and CF after cardioplegic arrest and ischemia by stimulation of NO production when given in the reperfusate after both 4 degrees C and 20 degrees C ischemia. However, L-arg as an additive to cardioplegia was only beneficial after 20 degrees C, and not after 4 degrees C ischemia.

Animals↗
PubMed1997

Functional and metabolic effects of adenosine in cardioplegia: role of temperature and concentration.

BACKGROUND: Addition of adenosine to cardioplegic fluid has been shown to improve myocardial tolerance to ischemia. This study was designed to investigate further this phenomenon to evaluate the dose-response and the temperature dependence of the effect of addition of adenosine to St. Thomas' Hospital cardioplegic solution. METHODS: The isolated working rat heart model was used in this study. After the assessment of control function, hearts (6 in each group) were subjected to infusions of cardioplegic solution containing 0.0 (control), 0.1, 5.0, 10.0 or 20.0 mmol/L adenosine followed by 3 hours of ischemic arrest at temperatures of 20 degrees C, 10 degrees C, or 4 degrees C with multidose (3 minutes every 30 minutes) cardioplegic infusion. RESULTS: After ischemic arrest at 20 degrees C, the recovery of cardiac output (expressed as percent of preischemic baseline) was 35.4 +/- 5.11 (control) 45.0 +/- 5.51 (0.1 mmol/L), 53.1 +/- 2.9 (5.0 mmol/L), 61.8 +/- 3.7 (10.0 mmol/L), and 57.6 +/- 2.3 (20.0 mmol/L). Hearts receiving 5.0 to 20.0 mmol/L adenosine had significantly greater recovery of cardiac output than control hearts. In its optimal concentration (10 mmol/L), adenosine improved the efficacy of the cardioplegic solution by almost 75%. Myocardial adenosine triphosphate content (expressed in mumol/g protein) was 4.7 +/- 0.5 (control), 4.9 +/- 1.4 (0.1 mmol/L), 8.1 +/- 0.7 (5 mmol/L), 12.5 +/- 2.0 (10 mmol/L), and 11.2 +/- 2.8 (20 mmol/L), at the end of ischemia and 13.9 +/- 0.2 (control), 13.1 +/- 1.7 (0.1 mmol/L), 18.0 +/- 2.0 (5 mmol/L), 18.6 +/- 1.2 (10 mmol/L), and 20.7 +/- 2.1 (20 mmol/L) at the end of reperfusion. Thus, the adenosine triphosphate content was higher (p < 0.05) in hearts receiving 5.0 to 20.0 mmol/L adenosine than in controls both at the end of ischemia and after reperfusion. Myocardial adenosine monophosphate level at the end of ischemia was inversely related to adenosine triphosphate level. Functional assessment of the effect of 10 mmol/L adenosine at 10 degrees C and 4 degrees C during arrest indicated attenuation of beneficial effects: adenosine improved function only by 17% at 10 degrees C, whereas at 4 degrees C the protective effect was not observed. CONCLUSIONS: These observations suggest that adenosine has the potential to enhance the efficacy of clinical cardioplegic arrest but the degree of improvement is lower at decreased temperature during ischemia. A principal mechanism of action of this modification of cardioplegic fluid appears to be through the inhibition of high-energy phosphate utilization immediately before or during ischemia.

Adenosine↗
PubMed1997

Inhibition of endogenous endothelin during cardioplegia improves low coronary reflow following prolonged hypothermic arrest.

OBJECTIVE: Endothelin-1 (ET) is a potent endogenous vasoconstrictor which has been shown to be increased following ischaemia and cardiopulmonary bypass. We tested the hypothesis that inhibition of ET synthesis during cardioplegic arrest using phosphoramidon (an ET converting enzyme inhibitor) or blockade of ET receptors using bosentan (a mixed ET(A)/ET(B) antagonist), might improve the postischaemic recovery of coronary flow. METHODS: Using an isolated Langendorff perfused rat heart model we compared the addition of phosphoramidon or bosentan to St Thomas' Hospital No. cardioplegia vs. control (plain cardioplegia). We measured recovery of coronary flow following 4 h of cardioplegic arrest at 4 degrees C. In a second series of experiments using an isolated working rat heart model we measured the recovery of cardiac function following 4 h of cardioplegic arrest at 4 degrees C. Results are expressed as percentages of preischaemic values (+/- S.E.M). RESULTS: In the first series of experiments, addition of phosphoramidon to cardioplegia improved the postischaemic recovery of coronary flow after 30 min of reperfusion: control 81.3% (+/- 3.5); phosphoramidon 10(-6) M 86.2% (+/- 3.1); phosphoramidon 10(-5) M 95.0% (+/- 3.0) P = 0.03 vs. control. Likewise, addition of bosentan 10(-5) M improved coronary flow following 20 min of reperfusion: control 96.7% (+/- 4.0), and bosentan 109.6% (+/- 4.7) P = 0.04. The addition of phosphoramidon or bosentan had no effect on the postischaemic recovery of mechanical function following 30 min of reperfusion. CONCLUSION: Both inhibition of ET synthesis and ET receptor blockade during prolonged hypothermic arrest improves postischaemic coronary flow, but appears to have no effect on the recovery of cardiac mechanical function.

Animals↗
PubMed1997

Effect of cardioplegia infusion pressure on coronary artery endothelium and cardiac mechanical function.

OBJECTIVE: Monitoring of cardioplegia infusion pressure may be important, particularly in immature hearts and in hearts without coronary artery disease. We have investigated the effects of infusion pressure on the preservation of the isolated rat heart. METHODS: Hearts (five in each group) were subjected to a single (20 ml) infusion of St. Thomas' Hospital cardioplegic solution at pressures of 60, 120, 180 and 240 cmH2O (44-176 mmHg), followed by 30 min of hypothermic (20 degrees C) ischemia. RESULTS: Mean recovery of cardiac output (expressed as a percentage of its preischemic value) decreased with increasing infusion pressure: 96.1 +/- 0.6%, 87.3 +/- 2.1% (P < 0.05 vs. 60 cmH2O), 79.3 +/- 2.8% (P < 0.05 vs. 120 cmH2O), 72.0 +/- 3.0% (not significant vs. 180 cmH2O), respectively. Endothelial function, as assessed by pre- and post-ischemic ability to secrete NO in response to 5-hydroxytryptamine, remained relatively normal after infusion at 60 cmH2O, but changed from vasodilation to vasoconstriction after infusion at 240 cmH2O. Electron microscopy revealed mild endothelial damage after infusion at 240 cmH2O, which was greatly exacerbated by reperfusion and was accompanied by regions of myocyte damage compatible with reperfusion of unprotected myocardium. The relationship between cardioplegia infusion pressure and infusion time was not linear and implied that infusion pressures greater than 120 cmH2O caused vascular smooth muscle constriction. CONCLUSIONS: These results suggest that even mildly raised cardioplegia infusion pressures may be detrimental to cardiac preservation and the effects are possibly mediated through endothelial damage and pressure-induced coronary vasoconstriction.

Animals↗