Infusion Of Isosorbide Dinitrate Research Articles

Prevention of contrast-induced nephropathy by adequate hydration combined with isosorbide dinitrate for patients with renal insufficiency and congestive heart failure.

Adequate hydration remains the mainstay of contrast-induced nephropathy prevention, and nitrates could reduce cardiac preload. This study aimed to explore the adequate hydration with nitrates for patients with chronic kidney disease (CKD) and congestive heart failure (CHF) to reduce the risk of contrast-induced nephropathy (CIN) and at the same time avoid the acute heart failure. Three hundred and ninty-four consecutive patients with CKD and CHF undergoing coronary procedures were randomized to either adequate hydration with nitrates (n = 196) or to routine hydration (control group; n = 198). The adequate hydration group received continuous intravenous infusion of isosorbide dinitrate combined with intravenous infusion of isotonic saline at a rate of 1.5 mL/kg/h during perioperative period. The definition of CIN was a 25% or 0.5 mg/dL rise in serum creatinine over baseline. This trial is registered with www.clinicaltrials.gov, number NCT02718521. Baseline characteristics were well-matched between the two groups. CIN occurred less frequently in adequate hydration group than the control group (12.8% vs 21.2%; P = 0.018). The incidence of acute heart failure did not differ between the two groups (8 [4.08%] vs 6[3.03%]; P = 0.599). Cumulative major adverse events (death, myocardial infarction, stoke, hospitalization for acute heart failure) during the 90-day follow-up were lower in the adequate hydration with nitrates group (P = 0.002). Adequate hydration with nitrates can safely and effectively reduce the risk of CIN in patients with CKD and CHF.

COMPARING BALLOON DIAMETER ON PERFORMING ENDOSCOPIC PAPILLARY BALLOON DILATATION WITH ISOSORBIDE DINITRATE DRIP INFUSION FOR REMOVAL OF BILE DUCT STONES

Background: Endoscopic papillary balloon dilatation (EPBD) is one of the methods to remove bile duct stones. EPBD might preserve the function of the sphincter of Oddi despite the potential risk of acute pancreatitis. There are only a few reports of EPBD reducing the risk of acute pancreatitis and, at same time, preserving the function of the sphincter of Oddi. Methods: We performed EPBD for bile duct stone removal in 60 patients using two balloons with different diameters. Patients were randomized to EPBD with a 6 mm balloon (n = 30) or an 8 mm balloon (n = 30). In both groups, isosorbide dinitrate (ISDN) was infused in a rate of 5 mg/h while low pressure EPBD were being performed. The pressure of the sphincter of Oddi was observed before and after the EPBD procedures. Also, serum amylase level after EPBD was observed for both groups. Results: Serum amylase level of the 6 mm group was significantly higher than that of the 8 mm group (P < 0.05). Acute pancreatitis occurred in two patients ( 6.7%) in the 6 mm group whereas no case was observed for the 8 mm group. The rates of duct clearance were 93% in the 6 mm group and 100% in the 8 mm group. Stone removals were difficult in seven cases with 6 mm balloon dilatations due to the narrow orifices of the papilla. In the 6 mm group, there was no significant difference between the basal sphincter of Oddi pressure (BSOP) and the phasic sphincter of Oddi pressure (PSOP) before and after EPBD. However in the 8 mm group, the BSOP observed after the EPBD procedure was significantly higher than BSOP before the treatments. Within this group, BSOP values after EPBD were preserved by approximately 80% of the BSOP values before the treatments. In contrast, there was no significant difference in PSOP before and after the treatments. Regarding the stone numbers, no significant difference was observed in BSOP before and after the treatments for the 6 mm group with less than two stones. Also, as for stone size, no significant difference was observed in BSOP before and after the treatments for the 6 mm group with stones of less than 6 mm in diameter. Conclusion: We are now conducting EPBD with ISDN infusion using a 6 mm balloon for a patient who has less than two stones with size not exceeding 6 mm in diameter. An 8 mm balloon is used for a patient with more than two stones or a stone greater than 6 mm in size.

Outpatient infusion of isosorbide dinitrate in patients with worsening chronic heart failure

Outpatient infusion of isosorbide dinitrate in patients with worsening chronic heart failure

Abstract 2571: Long-Term Endothelial Dysfunction after Coronary Artery Stenting with Drug-Eluting Stent Associated with Local Inflammatory Response

Endothelial function remains chronically abnormal after vascular injury associated with coronary intervention. The long-term effects of drug-eluting stent (DES) on endothelial function are not known. We evaluated the endothelial-dependent vasomotor function and local release of pentraxin3 (PTX3) as a local inflammatory marker in nonrestenotic coronary arteries more than six months following DES and bare metal stent (BMS) implantation. Fifty-two patients treated six months earlier with a coronary stenting for isolated proximal left anterior descending (LAD) stenosis, with no evidence of restenosis, were studied. Twenty patients had been stented with BMS, and 32 had been with DES. Changes in diameter at distal site of the stented LAD in response to intracoronary acetylcholine (Ach) infusions (1,3,10,30 μg/min) were assessed by quantitative angiography. At the completion of the protocol, a 2mg bolus of isosorbide dinitrate (ISDN) was injected into the LAD. We also measured serum PTX3 levels sampled in coronary sinus (CS) and sinus of Valsalva (V). Results: The two groups had similar risk factors for endothelial dysfunction. The mean percent change in the diameter of the stented LAD by Ach injection was significantly more in the DES group than in the BMS group (−38.9±6.1 vs. −19.2±6.7 %, p&lt;0.01). There was no significant difference in maximal dilation achieved by ISDN infusion between the two groups (34.6±6.6 vs. 31.2±4.6 %, NS). The translesional PTX3 gradient (CS-PTX3 minus V-PTX3) was higher in the DES group than in the BMS group (+0.11±0.05 vs. −0.01±0.05 ng/ml, p&lt;0.01). More severe endothelial dysfunction was observed long term after DES implantation as compared to BMS. These findings were associated with an increased local inflammatory response to DES stenting.

Ocular hemodynamic effects of nitrovasodilators in healthy subjects

Abstract Purpose: Previous studies on the ocular hemodynamic effects of nitrates showed partially contradicting results. The aim of the present study was to investigate the effect of nitrovasodilators on choroidal and optic nerve head (ONH) blood flow. Methods: The study was performed in a randomized, placebo‐controlled, double masked, 4‐way crossover design in 12 healthy male subjects. Nitroglycerine, isosorbide dinitrate or sodium nitroprusside were administered intravenously in stepwise increasing doses on different study days. Physiologic saline solution was used as placebo control. To assess choroidal and ONH microcirculation, laser Doppler flowmetry measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal and ONH blood flow. Ocular perfusion pressure (OPP) was calculated as OPP=2/3MAP‐IOP. Thereafter a parameter of vascular resistance (R) for each measured blood flow parameter (BF) was calculated as R~OPP/BF. Results: Placebo administration did not change any of the measured parameters. We observed small but significant reduction of IOP during the infusion of sodium nitroprusside. The pulsatile choroidal blood flow decreased significantly during the infusion of isosorbide dinitrate (–8.1%) and sodium nitroprusside (–4.3%). The pulsatile ONH blood flow decreased significantly only during the infusion of sodium nitroprusside (–5.7%). In addition, we observed a significant reduction of all calculated parameters of vascular resistance during the infusion of each nitrovasodilator (maximal decrease: –16% to –29%). Conclusions: An intravenous infusion of nitroglycerine, isosorbide dinitrate or sodium nitroprusside caused a significant reduction of vascular resistance in the ONH and the choroid.

Drug-Eluting Stents Versus Coronary Artery Bypass Grafting in Patients with Diabetes Mellitus

Reduction of restenosis and reinterventions was recently reported with percutaneous interventions (PCI) with drug-eluting stents (Cypher). This study compares results of Cypher (Cordis, Miami Lakes, FL) stenting and surgical revascularization in diabetic patients. From January 2002 to January 2005, 518 consecutive diabetic patients underwent myocardial revascularization; 176 by PCI incorporating Cyphers and 342 treated surgically. Single-vessel patients in the surgical group were treated with the left internal thoracic artery (ITA) and most multivessel patients were treated with two ITAs. After matching for age, sex, right system revascularization, and extent of coronary disease, two groups (86 patients each) were used to compare the two revascularization modalities. Both groups were similar; however, left main, poor ejection fraction, total occlusion, and bifurcation lesions were more prevalent in the surgical group, and in-stent restenosis in the PCI group. The mean number of coronary vessels treated was higher in the surgical group (2.05 vs 1.6, p < 0.001). Mean follow-up was 18 months. Overall mortality (early and late) was 2.3% and 3.5% in the Cypher and surgical groups, respectively (p = 0.65). Angina returned in 39.5% of the Cypher group and 15.1% of the surgical group, p < 0.001. There were 25 reinterventions in the Cypher group compared with five in the surgical group (p = 0.010). The Cox proportional hazard model revealed assignment to the Cypher group to be the only independent predictor of reangina (odds ratio [OR] 3.26, 95% confidence interval [CI] 1.63 to 6.53) and reintervention (OR 4.17, 95% CI 1.92 to 20.83). Despite improved results of PCI with Cyphers, midterm clinical outcome of diabetic patients treated surgically is better.

Safeguards against acute pancreatitis associated with endoscopic papillary balloon dilatation

Endoscopic papillary balloon dilatation (EPBD) is one of the methods used to remove bile duct stones. EPBD may preserve the function of the sphincter of Oddi in spite of the potential risk of acute pancreatitis caused by the procedure. There are only few reports of attempts to reduce the risk of acute pancreatitis in EPBD. We performed EPBD for bile duct stone removal in 201 patients. We used an 8-mm balloon followed by drip infusion of isosorbide dinitrate (ISDN) at a rate of 5 mg/h for low-pressure EPBD. The function of the minor duodenal papilla, the inflation pressure required for the disappearance of the notch sign in the bile duct, and the serum amylase level after EPBD were observed. The median serum amylase level after the procedure was 367 IU/l. Acute pancreatitis occurred in two patients (1.0%). The two patients with acute pancreatitis had poor function of the minor duodenal papilla, a high inflation pressure (over 5 atm) required for disappearance of the notch, sign, and severe abdominal pain during balloon inflation; as well, the procedure took a long time. The rate of duct clearance was 99.5%. EPBD with gradual inflation of the balloon at a low pressure, followed by ISDN drip infusion, could decrease the risk of acute pancreatitis associated with the procedure. Poor function of the minor duodenal papilla, high inflation pressure required for disappearance of the notch, sign, severe abdominal pain, and a lengthy procedure increase the risk of acute pancreatitis after EPBD.

Insulin resistance relates to acetylcholine-induced microvascular vasoconstriction in a patient with vasospastic angina: potential implication of causalities between hyperinsulinemia and coronary microcirculation failure

Coronary vasomotor response to acetylcholine infusion was studied in a 69-year-old currently smoking man with enhanced insulin response to oral glucose load. Coronary angiogram showed no significant stenoses. Immediately after 20 microg acetylcholine infusion in the right coronary artery, angiographic no-flow, ischemic electrocardiographic changes, and anginal pain developed in the absence of epicardial coronary obstruction. While intracoronary infusion of isosorbide dinitrate was only partially effective, intracoronary infusion of nicorandil, an agent known to improve coronary microcirculation, completely resolved these changes. This is the first case reported so far suggesting that enhanced insulin response may be associated with acetylcholine-induced microvascular vasoconstriction. Microvascular vasoconstriction must be considered when a patient with insulin resistance presents with chest pain.

COMPARING BALLOON DIAMETER ON PERFORMING ENDOSCOPIC PAPILLARY BALLOON DILATATION WITH ISOSORBIDE DINITRATE DRIP INFUSION FOR REMOVAL OF BILE DUCT STONES

Background: Endoscopic papillary balloon dilatation (EPBD) is one of the methods to remove bile duct stones. EPBD might preserve the function of the sphincter of Oddi despite the potential risk of acute pancreatitis. There are only a few reports of EPBD reducing the risk of acute pancreatitis and, at same time, preserving the function of the sphincter of Oddi.Methods: We performed EPBD for bile duct stone removal in 60 patients using two balloons with different diameters. Patients were randomized to EPBD with a 6 mm balloon (n = 30) or an 8 mm balloon (n = 30). In both groups, isosorbide dinitrate (ISDN) was infused in a rate of 5 mg/h while low pressure EPBD were being performed. The pressure of the sphincter of Oddi was observed before and after the EPBD procedures. Also, serum amylase level after EPBD was observed for both groups.Results: Serum amylase level of the 6 mm group was significantly higher than that of the 8 mm group (P &lt; 0.05). Acute pancreatitis occurred in two patients ( 6.7%) in the 6 mm group whereas no case was observed for the 8 mm group. The rates of duct clearance were 93% in the 6 mm group and 100% in the 8 mm group. Stone removals were difficult in seven cases with 6 mm balloon dilatations due to the narrow orifices of the papilla. In the 6 mm group, there was no significant difference between the basal sphincter of Oddi pressure (BSOP) and the phasic sphincter of Oddi pressure (PSOP) before and after EPBD. However in the 8 mm group, the BSOP observed after the EPBD procedure was significantly higher than BSOP before the treatments. Within this group, BSOP values after EPBD were preserved by approximately 80% of the BSOP values before the treatments. In contrast, there was no significant difference in PSOP before and after the treatments. Regarding the stone numbers, no significant difference was observed in BSOP before and after the treatments for the 6 mm group with less than two stones. Also, as for stone size, no significant difference was observed in BSOP before and after the treatments for the 6 mm group with stones of less than 6 mm in diameter.Conclusion: We are now conducting EPBD with ISDN infusion using a 6 mm balloon for a patient who has less than two stones with size not exceeding 6 mm in diameter. An 8 mm balloon is used for a patient with more than two stones or a stone greater than 6 mm in size.

Continuous administration of organic nitrate decreases hepatic cytochrome P450.

We previously reported that cytochrome P450 (P450) is a key enzyme of organic nitrate biotransformation and that P450 levels of the heart and its vessels markedly decreased at the development of nitrate tolerance. Although our attention was mainly focused on the circulatory organs, most organic nitrates, including nitroglycerin (NTG), are metabolized in the liver, where nitric oxide (NO) is concomitantly produced from the organic nitrates. NO reacts with various molecules such as superoxide, heme, thiols, and oxygen. This paper examined whether hepatic P450 levels are also affected after organic nitrate administration, since the liver is the major organ of P450 related metabolism. Male Wistar rats were intravenously administrated NTG or isosorbide dinitrate (ISDN) for 24-96 h. We observed the level of hemeoxygenase-1 (HO-1) as the functional marker of hepatic P450, since one of the acute phase target proteins of NO induction is an inducible type of HO-1. Hepatic P450 was drastically decreased after 48 or 72 h of continuous NTG or ISDN infusion, when nitrate tolerance was observed, but it recovered 48 h after cessation of the NTG administration. HO-1 was induced within 24 h of continuous NTG infusion, but it returned to normal levels 48 h after cessation of NTG. The administration of sodium nitroprusside, an agent to which the animals showed no tolerance, did not induce HO-1 or P450 depletion. Chronic administration of organic nitrates significantly decreased hepatic P450. These results suggest that P450-dependent drug metabolism may be drastically affected after continuous organic nitrate administration.

A Ratio of Arterial Oxygen Tension to Inspired Oxygen Fraction (PaO2/FiO2 ratio) after Cardiopulmonary Bypass in Coronary Artery Bypass Graft Surgery: Amrinone-Dopamine versus Isosorbide Dinitrate-Dopamine

Background: Cardiopulmonary bypass (CPB) may produce lung injury with decreased PaO/FiO ratio in patients undergoing CABG surgery. We examined PaO/FiO ratio and incidence of PaO/FiO ＜ 300 or 150 to determine the differences in oxygenation with the use of amrinone-dopamine (DP) or isosorbide dinitrate (IDN)-DP in patients undergoing CABG. Methods: Twenty patients undergoing elective CABG were divided into two groups according to drug used on separation from CPB: IDN-DP (Group 1, n = 10) or amrinone-DP (Group 2, n = 10). Anesthesia was induced and maintained with propofol, fentanyl and vecuronium. IDN infusion (1.0g/kg/min) was started preoperatively in both groups. Mild hypothermic CPB was applied with a roller pump and nonpulsatile flow maintained a mean arterial pressure of 60-80 mmHg. In Group 2, amrinone was administered (0.75 mg/kg + 10g/kg/min) instead of IDN at the time of CPB separation. DP infusion (3g/kg/min) was started at a rectal temperature more than 35.5 and adjusted to maintain acceptable hemodynamics. IDN-DP or amrinone-DP infusion, monitoring and sedation with propofol were continued in the intensive care unit (ICU). PaO/FiO ratio under controlled ventilation with air/O mixture (FiO 0.6) was checked immediately before CPB (pre-CPB), 30 mins (post-CPB), 60 mins after CPB (post-CPB) and 30 mins after admission to ICU (ICU). Results: There was no significant difference between the groups in the terms of the duration of arotic cross clamp, PaO/FiO at pre-CPB, PaO/FiO at post-CPB, PaO/FiO at ICU or in the incidence of PaO/FiO ＜ 150, PaO/FiO ＜ 300 at ICU. But there was a significant difference in PaO/FiO post CPB (263.3 105.5 in Group 1 vs. 381.7 69.5 in Group 2, P ＜ 0.05). Conclusions: Amrinone-DP provides more favorable oxygenation immediately after CPB in CABG surgery than IDN-DP.

Potentiation of sildenafil-induced hypotension is minimal with nitrates generating a radical intermediate.

Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. Because of the phosphodiesterase-5 inhibitor-induced increases of cyclic GMP in the vasculature, vasodilation in various vascular beds is induced, which in combination with various nitrovasodilators (e.g., when used simultaneously for the treatment of coronary artery disease), may lead to excessive hypotension. Thus nitrovasodilators are contraindicated when sildenafil may be used and reports of a number of accidents have recently been published. We therefore studied the acute interactions of glyceryl trinitrate (GTN), pentaerythritol tetranitrate (PETN), and isosorbide dinitrate (ISDN) with sildenafil in six chronically instrumented conscious dogs for each nitrate to assess the magnitude of blood pressure drops (and compensatory increases in heart rate) during a 24-h nitrate administration (infusion into the pulmonary artery). Sildenafil (3 mg/kg) was given orally (after a 24-h fast) 30 min after start of nitrate infusion. GTN, PETN, or ISDN (which follow different steps of metabolic conversion to nitric oxide) were applied at submaximal dosages leading to 90% of maximal coronary artery dilation at 1.5 microg/kg per min, 0.75 microg/kg per min, or 6 microg/kg per min, respectively. During GTN infusion sildenafil caused a maximum drop in mean blood pressure of 21 +/- 3 mm Hg (rise in heart rate from 117.0 +/- 7.2 to 126.0 +/- 6 .0/min) and during ISDN infusion of 18 +/- 3 mm Hg (rise in heart rate from 115.0 +/- 7.0 to 125 +/- 6/min), which was significantly less (p < 0.01) during PETN (only 6 +/- 1 mm Hg with a rise in heart rate from 107.0 +/- 5.0 to 122.0 +/- 7.0/min). When sildenafil is used during exposure to nitrates (e.g., in coronary artery disease), the PETN-induced drop in blood pressure at equi-effective dosages (with regard to coronary dilation) is substantially smaller compared with that of GTN or ISDN, which is probably because of lesser potentiation of phosphodiesterase-5 inhibitor-induced effects in the arteriolar bed, thus minimizing critical drops in blood pressure.

Treatment of acute pulmonary oedema: diuresis or vasodilatation?

Intravenous loop diuretics have formed the mainstay of treatment for acute cardiogenic pulmonary oedema since the 1960s but in recent years increasing use has been made of intravenous nitrates as adjunctive therapy for acute and chronic pulmonary oedema. In 1973 Chatterjee and colleagues1 reported potentially beneficial effects of nitroprusside infusion in patients with acute myocardial infarction and high left-ventricular filling pressures and raised the possibility of lowering mortality. In 1983 Nelson and colleagues2 reported a randomised, prospective study of isosorbide dinitrate infusion versus furosemide infusion that showed similar falls in pulmonary-artery occluded pressure (equivalent to leftatrial pressure) and suggested that isosorbide dinitrate resulted in haemodynamically better changes with regard to myocardial oxygen consumption and peripheral perfusion.

Effects of Isosorbide Dinitrate(Isoket(R)) on Coronary Perfusion Pressure during the Cardiopulmonary Resuscitation

Background : Coronary perfusion pressure(CPP) is the most important factor for the success of cardiopulmonary resuscitation(CPR). Therefore, CPP must be optimized during the resuscitation. The purpose of this study is to investigate the effects of isosorbide dinitrate(Isoket ) on CPP during CPR. Methods : 10 Korean dogs were divided into two groups: Group I(N=5) was resuscitated with infusion of isosorbide dinitrate(1 g /kg/min) and Group II(N=5) was resuscitated without using isosorbide dinitrate. Following CPR, the heart rate(HR), blood pressure(BP), pulmonary capillary wedge pressure, cardiac output(CO), CPP and endocardial viability ratio(EVR) were measured repeatedly. Results : The changes in HR were not significantly different between the two groups but systolic and diastolic BP, CO, CPP and EVR were well maintained in group 1. Conclusions : These results suggest that the usual dosage of isosorbide dinitrate is effective in improving CPP and EVR on CPR after impending cardiac arrest. (Korean J Anesthesiol 1998; 35: 252∼258)

Comparison of endoscopic papillary balloon dilation with infusion of isosorbide dinitrate and endoscopic sphincterotomy in the treatment of common bile duct stones

Comparison of endoscopic papillary balloon dilation with infusion of isosorbide dinitrate and endoscopic sphincterotomy in the treatment of common bile duct stones

Endoscopic Papillary Dilation by Balloon and Isosorbide Dinitrate Drip Infusion for Removing Bile Duct Stone

Background: Endoscopic papillary dilation (EPD) by balloon in the management of bile duct stones has recently been claimed to be effective for removing bile duct stones. Methods: Without endoscopic sphincterotomy, we attempted to remove large or multiple bile duct stones through EPD combined with drip infusion of isosorbide dinitrate in 35 patients. Isosorbide dinitrate, at a rate of 5 mg/h, was administered intravenously, and a balloon dilator with a 10-mm diameter was inflated within 3 min across the papilla. Stones were then smashed using a mechanical lithotriptor, and the fragments were extracted with a basket or the balloon. Results: Extraction of stones was successful in 33 (94%) of 35 patients by the combined therapy. Two of them (6%) developed mild pancreatitis. Conclusion: EPD combined with medical sphincter dilation was effective for large and multiple bile duct stones.

Pharmacokinetics of isosorbide dinitrate in healthy volunteers after 24-hour intravenous infusion.

No studies have examined the pharmacokinetics of isosorbide dinitrate (ISDN) after infusion of long duration, even though such infusions are used in patients. We therefore measured ISDN and its active metabolites, isosorbide-5-mononitrate (IS5MN) and isosorbide-2-mononitrate (IS2MN), in plasma of 9 healthy volunteers who received a continuous intravenous infusion of ISDN for 24 hours at a dose rate that lowered diastolic blood pressure by 10% during the first 30 minutes of infusion. All subjects tolerated the infusion except one who experienced intolerable headache. Five subjects received 1 microgram.min-1.kg-1, one 2 micrograms.min-1.kg-1, and two 4 micrograms.min-1.kg-1 ISDN, whereas the full rate of 6 micrograms.min-1.kg-1 was used continuously in one subject. At all infusion rates the plasma concentrations of ISDN were higher at 24 hours than at earlier times, suggesting that a steady-state condition had not been reached at that time. The same was true for the mononitrate metabolites, which reached higher plasma concentrations and were cleared more slowly than the parent compound after the end of the infusion. Apparent elimination half-lives of ISDN, IS2MN, and IS5MN were 67 +/- 10 minutes, 115 +/- 13 minutes, and 272 +/- 38 minutes, respectively. Comparison of low-rate infusions (1 and 2 micrograms.min-1.kg-1) with high-rate infusions (4 and 6 micrograms.min-1.kg-1) showed that the plasma concentration ratios at 24 hours of mononitrate metabolites to parent drug and apparent plasma clearance of ISDN were almost halved at the higher infusion rates.

Quantitative analysis of technetium 99m 2-methoxyisobutyl isonitrile single-photon emission computed tomography and isosorbide dinitrate infusion in assessment of myocardial viability before and after revascularization

Background. Assessment of viable myocardium in territories of hypoperfused myocardium is important for predicting functional recovery after revascularization. This study was designed to evaluate quantitative analysis of 99mTc-labeled 2-methoxyisobutyl isonitrile (MIBI) myocardial perfusion imaging combined with isosorbide dinitrate (ISDN) infusion to detect myocardial viability in patients with chronic coronary artery disease before and after revascularization. Methods and Results. Twenty-seven consecutive patients with previous myocardial infarction and left ventricular dysfunction (left ventricular ejection fraction 35.2% ± 13.5%) referred for coronary artery bypass (CABG) were studied with 99mTc-labeled MIBI single-photon emission computed tomograpy at rest and during ISDN infusion before CABG followed by resting imaging after CABG. Quantitative analysis was performed with circumferential profiles. Left ventricular function (global and regional) was assessed by radionuclide ventriculography before and after CABG. Out of 212 abnormal perfusion segments with resting 99mTc-labeled MIBI SPECT, 99 segments (47%) showed improved uptake of 99mTc-labeled MIBI during ISDN infusion. The mean ratio of myocardial uptake was 0.58 ± 0.25 (resting 0.53 ± 0.23; p < 0.05). After CABG, of 212 segments with hypoperfusion, 108 segments (51%; p > 0.05 vs ISDN) showed improved uptake of 99mTc-labeled MIBI. The mean ratio of myocardial uptake was 0.60 ± 0.26 (resting 0.53 ± 0.23; p < 0.05). The concordance between the improvement of post-CABG wall motion and that of pre-CABG ISDN perfusion imaging was 83%, between the improvement of wall motion and perfusion imaging after CABG 94%, and between the improvement of pre-CABG ISDN and post-CABG perfusion imaging 83%, respectively. Conclusion. ISDN infusion can improve the uptake of 99mTc-labeled MIBI in hypoperfused myocardium and increase the efficiency of 99mTc-labeled MIBI in the detection of viable myocardium in patients with previous myocardial infarction and left ventricular dysfunction.

The value of Tc-99m MIBI SPECT during isosorbide dinitrate infusion in assessment of viable myocardium in patients with myocardial infarction.

Tc-99m MIBI myocardial SPECT has shown promise for evaluation of coronary artery disease. But its role in predicting myocardial viability is still under investigation. The purpose of this study was to evaluate the value of Tc-99m MIBI myocardial SPECT during isosorbide dinitrate (ISDN) infusion in the assessment of myocardial viability. Thirty-seven patients with previous myocardial infarction (the infarct age ranged from < or = 30 days to 900 days) were studied, of them 13 patients had Tc-99m MIBI studies before and after coronary artery bypass grafting (CABG). The results showed that out of 134 segments with hypoperfusion at resting SPECT, 56 segments (41.8%) had an increase in Tc-99m MIBI uptake during ISDN infusion. Among them, 17 segments (30.4%) were normalized, 6 segments (10.7%) were significantly improved and 33 segments (58.9%) were improved. The degree of improvement in perfusion was related to the age of the myocardial infarction. In 13 patients with CABG, of 31 segments with improvement in perfusion post CABG, 25 segments (80.6%) showed perfusion improvement during ISDN infusion, and of 28 segments with improved wall motion post CABG, 23 segments (82.1%) showed improvement in perfusion during ISDN infusion. Tc-99m MIBI SPECT during ISDN infusion may therefore be a useful approach for assessing myocardial viability.

Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis.

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26 dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg), systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g), portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.