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Biomedical subjects

G Fragasso

Publications and source records attributed to G Fragasso.

At least 37 records · Page 2Linked to original sources
PubMed1998

Septal panniculitis induced by atenolol--a case report.

The authors report a case of septal panniculitis induced by atenolol in a patient with coronary artery disease. Several tender, erythematous, suppurated subcutaneous nodules appeared over the metacarpal-phalanx and interphalanx joints of both hands. Hematology indicated a transient inflammatory immunomediated disorder, with an increase of cytotoxic suppressor lymphocytes and presence of antinuclear antibodies. The dramatic inflammatory involvement of the subcutaneous connective tissue could have eventually progressed toward fibrosis, if atenolol had not been withdrawn. This raises the possibility that retroperitoneal fibrosis, a recognized adverse effect of beta blockers, may just represent the terminal phase of undetected connective tissue inflammation occurring in districts not easily explorable before overt manifestations of the disease. Since retroperitoneal fibrosis has already been associated with migratory panniculitis and described as mesenteric panniculitis, it is tempting to speculate that these manifestations originate from the same mechanisms.

Adrenergic beta-Antagonists↗
PubMed1998

[Role of stress myocardial perfusion scintigraphy in the follow-up of patients undergoing coronary angioplasty: comparison between qualitative and semi-quantitative analysis].

In order to assess the diagnostic accuracy of stress/rest myocardial perfusion scintigraphy in the follow-up of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) we studied 50 patients (pts) before and 6 months after PTCA. All patients underwent control coronary angiography and then were divided in 2 groups, according to angiographic evidence of restenosis (25 pts) or no restenosis (25 pts). Myocardial perfusion imaging was performed with 99mTc-methoxy-isobutyl-isonitrile (MIBI). For MIBI scans, both qualitative and semi-quantitative analysis were performed. SPECT images were displayed on a color monitor in random order and graded blindly by 2 experienced observers. Rest and stress MIBI uptake was scored using a 4-point scale (ranging from 0 = normal, to 3 = absence of uptake). Individual subjects' perfusion scores were calculated by adding the individual segments' scores. History of relapsing angina showed a sensitivity and specificity of 76 and 96%, respectively. Exercise testing and MIBI tomoscintigraphy exhibited sensitivity and specificity of 80 and 56%, and 92 and 44%, respectively. However, when considering semiquantitative data and comparing them with pre-PTCA studies, specificity of MIBI scan increased to 96%, while sensitivity decreased to 72%. The results of the present study confirm high sensitivity and low specificity for both exercise ECG and myocardial perfusion scintigraphy, in the detection of restenosis following PTCA. However, when performing semiquantitative analysis of perfusion scanning and comparison with pre-PTCA images, the specificity of MIBI tomoscintigraphy increases significantly. Therefore, when adopting myocardial perfusion scintigraphy for the follow-up of patients undergoing PTCA, a pre-revascularization scan should be obtained as often as possible. This approach, in the context of a positive test, makes feasible the assessment of often partial improvements in perfusion of the myocardium relative to the treated vessel, consequently avoiding many false positive results which invariably lead to coronary angiography.

Aged↗
PubMed1998

Differential effects of selective beta-adrenergic blockade on insulin sensitivity and release in control subjects and in patients with angina and normal coronary arteries (syndrome X).

AIMS: Betablockers are very effective in patients with angina and angiographically smooth coronary arteries (syndrome X), but may exacerbate the state of insulin resistance that is known to be present in such patients. The aim of the study was to evaluate the effects of short-term treatment with atenolol on carbohydrate metabolism in syndrome X patients, as compared to normal subjects. METHODS AND RESULTS: Seventeen patients (15 females, 55 +/- 8 years, BMI 23.4 +/- 2.7 kg/m2) and 11 controls (5 females, 50 +/- 7 years, BMI 23.1 +/- 2.0 kg/m2) were studied twice by an intravenous glucose tolerance test (IVGTT, 0.5 g/kg) after ten days of both placebo and atenolol (100 mg o.d.), given in random order. Metabolic indices measuring glucose effectiveness and insulin sensitivity were derived from minimal model analysis of the glucose and insulin profiles measured during the IVGTT. Indices of first- and second-phase insulin release were also calculated from the IVGTT insulin response. Atenolol had different metabolic effects on normal subjects and syndrome X patients. Despite the fact that the drug was found to be effective in relieving symptoms of chest pain, it induced a significant (p < 0.05) worsening of insulin resistance in syndrome X patients. No such effect was observed in control subjects. On the other hand, atenolol produced a marked reduction (40%, p < 0.05) of first-phase insulin release in control subjects, but no significant change of the same index in syndrome X patients. CONCLUSION: These results show that betablockers are very effective for controlling symptoms and improving quality of life in syndrome X patients. However, they appear to further impair the ability to dispose glucose. Long-term studies on the net effects of beta-blockade administration for the treatment of such patients are warranted.

Administration, Oral↗
PubMed1997

Myocardial viability assessed with fluorodeoxyglucose and PET in patients with Q wave myocardial infarction receiving thrombolysis: relationship to coronary anatomy and ventricular function.

In previously thrombolysed patients, we analysed residual myocardial viability using the PET-FDG technique and correlated its presence and extent to the angiographic appearance of the infarct-related vessel and left ventricular function. Thirty-six patients who had undergone intravenous thromboloysis for acute myocardial infarction 4.8 +/- 7.2 months previously were studied. Coronary angiography, left ventriculography, and assessment of myocardial perfusion and metabolism were all performed within 1 week. All patients exhibited perfusion defects consistent with the clinically identified myocardial infarction site. Residual viability, as assessed by the PET-FDG technique, was present in 53% of cases. The infarct-related coronary artery was patent in 19 (53%) patients (TIMI grade 3, 79%); of the remaining 17 with occluded infarct-related arteries, 11 had collaterals to the infarct area. Significant FDG uptake was observed in 63% of patients with a patent infarct-related artery and in 41% of those with an occluded infarct-related artery. The same study protocol was adopted in a control group of 30 patients with myocardial infarction who did not receive thrombolysis. The number of infarct-related patent vessels was significantly lower in these patients (30 vs 53%) (TIMI grade 3, 56%), but the overall percentage of PET viability was again 53%. Qualitative analysis of the regional perfusion pattern showed that the magnitude and severity of the perfusion defect was similar in the two groups, regardless of the presence or absence of FDG uptake. Global left ventricular function was also similar in the two groups. However, regional wall motion was significantly better in the thrombolysed patients with a patent infarct-related artery than in those who had not received thrombolysis and whose culprit vessel was also patent. In conclusion, the results of our study support the notion that early recanalization of the infarct-related artery is critical for preserving left ventricular function. Although the number of patent infarct-related coronary arteries is greater and left ventricular function is better in successfully thrombolysed patients, the regional metabolic pattern does not apparently correlate with the patency of the infarct-related artery. This suggests that, in "chronic' myocardial infarction, residual tissue viability as assessed by fluorodeoxyglucose uptake does not necessarily correlate with coronary recanalization.

Blood Glucose↗
PubMed1997

Impaired left ventricular filling dynamics in patients with angina and angiographically normal coronary arteries: effect of beta adrenergic blockade.

OBJECTIVE: To assess exercise performance and resting left ventricular filling dynamics in patients with syndrome X (SX) in basal conditions and after 10 days treatment with oral atenolol. DESIGN AND PATIENTS: Exercise performance was studied and left ventricular filling assessed by Doppler-derived transmitral flow pattern analysis in 22 patients (16 female, mean (SD) age 53 (4) years) with angina, a positive exercise test, and angiographically smooth coronary arteries. Patients were studied after two 10 day treatment periods with either atenolol or placebo in a single-blind, randomised, crossover trial. The same protocol was followed in 10 patients with documented coronary artery disease (CAD) and in 13 controls (C). RESULTS: Unlike the controls, patients with SX and those with CAD consistently showed exercise-induced ST segment abnormalities and impaired resting left ventricular filling while on placebo. Atenolol significantly reduced episodes of angina, completely prevented exercise-induced ST segment changes in 18 SX patients, and delayed their onset in all patients with CAD: in both groups the agent significantly improved Doppler-derived indices (mean (SD)) of ventricular filling (E/A 0.97 (0.27) v 1.22 (0.32) and 0.84 (0.21) v 1.19 (0.37), respectively). CONCLUSIONS: The objective documentation of left ventricular filling abnormalities may be useful in confirming the clinical diagnosis of SX and in providing objective evidence of therapeutic benefit. The similarity of the symptoms and electrocardiographic and ventricular filling abnormalities found in patients with SX and in those with CAD suggests that ischaemia is involved in both groups.

Adrenergic beta-Antagonists↗
PubMed1997

Abnormal myocardial glucose handling in patients with syndrome X: effect of beta-adrenergic blockade.

The present study was designed to test the hypothesis that patients with angina, positive exercise test and angiographically smooth coronary arteries (syndrome X), may exhibit abnormal myocardial glucose handling, as assessed by fluorodeoxyglucose (FDG) and positron emission tomography (PET) and to investigate the possibility that this abnormality could be reversed by treatment with betablockers, the drugs of choice in most patients with syndrome X. Eight consecutive patients (4 females, age 53 +/- 4 yrs) with syndrome X were studied. Off therapy, they underwent stress/rest 99m-TcMIBI SPET (360 degrees) and assessment of resting glucose metabolism by PET. PET studies were again performed after a 10 day treatment period on oral atenolol (100 mg/o.d.). All patients exhibited significant fasting FDG uptake in 2 or more myocardial regions. Overall, there were 28 of 48 segments (58%) with abnormal tracer uptake. On atenolol, there were only 5 segments with persistent FDG uptake (10%) in 2 patients. At rest, 7 patients exhibited perfusion defects in 14 myocardial segments. With stress performed in pharmacological wash-out, 5 patients developed perfusion defects in 10 myocardial segments. Eight of these segments were already underperfused at rest, and showed further reduction in perfusion after stress. All hypoperfused segments showed abnormal FDG uptake when the PET study was performed off therapy. The results suggest that, in patients with syndrome X, imbalance of the demand/supply ratio, either caused by limited coronary flow reserve or by primary vasoconstriction with reduction in myocardial perfusion, may determine a sustained metabolic shift towards anaerobic glycolysis. The mechanism by which atenolol improves metabolism in these patients could be simply related to reduction in O2 consumption.

Adrenergic beta-Antagonists↗
PubMed1996

Exercise-induced ischemic arrhythmias in patients with previous myocardial infarction: role of perfusion and tissue viability.

OBJECTIVES: This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias. BACKGROUND: We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates. METHODS: We studied 60 patients with chronic stable angina and a previous myocardial infarction. All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner. RESULTS: With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (> 10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not. The severity of coronary artery disease (Gensini score) was similar in the two groups. Postexercise SPECT showed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003). CONCLUSIONS: In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area.

Case-Control Studies↗
PubMed1996

Plasma nitrate plus nitrite changes during continuous intravenous infusion interleukin 2.

Nitric oxide (NO), a biologically active mediator generated in many cell types by the enzyme NO synthase, may play an important role in cardiovascular toxicity that is frequently observed in cancer patients during intravenous (i.v.) interleukin 2 (IL-2) therapy. The induction of NO synthase and the production of NO seem to be involved in the pathogenesis of the vascular leakage syndrome, as well as in the regulation of myocardial contractility. In the present study, we evaluated the pattern of plasmatic NO changes during multiple cycles of continuous i.v. infusion (CIVI) of IL-2 in ten advanced cancer patients (five males, five females, median age 59 years, range 33-67 years; eight affected by renal cell cancer and two affected by malignant melanoma). The patients received IL-2 at 18 MIU m-2 day-1 (14 cycles) or 9 MIU m-2 day-1 (seven cycles) for 96 h, repeated every 3 weeks. Interferon alpha (IFN alpha) was also administered subcutaneously (s.c) during the 3 week interval between IL-2 cycles. For each cycle, plasma samples were collected before treatment (t0), 24 h (t1), 48 h (t2), 72 h (t3) and 96 h (t4) after the start of IL-2 infusion, and 24 h after the end of the cycle. NO concentration was determined spectrophotometrically by measuring the accumulation of both nitrite and nitrate (after reduction to nitrite). The following observations may be drawn from data analysis: (1) plasma nitrate + nitrite significantly raised during treatment (P = 0.0226 for t0 vs t3), but statistical significance was retained only when cycles administered with IL-2 18 MIU m-2 day-1 are considered (P = 0.0329 for t0 vs t3; P = 0.0354 for t0 vs t2 vs t4) (dose-dependent pattern); (2) during subsequent cycles a significant trend toward a progressive increase of plasma nitrate + nitrite levels, with increasing cumulative dose of IL-2, was observed (linear regression coefficient r = 0.62, P = 0.0141 for t0; r = 0.80, P = 0.0003 for t1; r = 0.62, P = 0.013 for t2; r = 0.69, P = 0.045 for t3); (3) plasma nitrate + nitrite levels peaked earlier in subsequent cycles than in the first cycle; (4) all patients experienced hypotension. The mean of the systolic blood pressure values was significantly lower at the time of plasma nitrate + nitrite peak than at t0 (P = 0.0004); (5) the two cases of grade III hypotension occurred in patients with the higher mean and peak plasma nitrate + nitrite values. We conclude that determination of plasma nitrate + nitrite levels during CIVI IL-2 can usefully estimate, in a dose-dependent pattern, the degree of peripheral vascular relaxation and capillary leakage associated with cytokine action, clinically manifested as hypotension. However, isolated cardiac toxicity that continues to represent a relevant problem during IL-2 therapy, does not appear to correlate with plasma nitrate + nitrite levels; therefore, further studies are required to understand adequately the mechanisms underlying IL-2-induced cardiac toxicity.

Adult↗
PubMed1996

Angina with normal coronary arteries: diagnosis, pathophysiology and treatment.

Approximately 20% of patients undergoing diagnostic coronary arteriography for acute or chronic cardiac ischaemia have angiographically normal coronary arteries. The mechanism behind this phenomenon is likely to be the result of a combination of functional or anatomical abnormalities in the coronary microcirculation, a metabolic disorder which affects the handling of energy substrates by the heart, insulin resistance and a neurological component affecting pain perception. Indeed, it has been demonstrated that these patients often exhibit an increase in sympathetic outflow to the cardiovascular system, which might account for the reduction in coronary flow reserve, changes in metabolic utilization and development of insulin resistance that are seen in some of these patients. Therapeutically, beta-blockers appear to be most effective in controlling the symptoms associated with this condition, although those calcium antagonists which do not affect the neurohormonal system may be of some utility in patients with primary microvascular angina, in which microvascular spasm is operating or in whom excessive constriction of the distal component of the coronary circulation limits the vasodilatory reserve.

Adrenergic beta-Antagonists↗
PubMed1996

High prevalence of the thallium-201 reverse redistribution phenomenon in patients with syndrome X.

OBJECTIVE: To evaluate the stress-myocardial perfusion pattern in patients with angina, positive exercise test and angiographically smooth coronary arteries (syndrome X). DESIGN: Prospective study. PATIENTS AND METHODS: Twenty-five consecutive patients (seven males, mean age 54 +/- 8 years) with typical angina, positive exercise test, normal coronary arteries and no inducible spasm, underwent stress-redistribution thallium-201 myocardial perfusion scintigraphy. Thirty-two consecutive patients (14 males, mean age 49 +/- 7 years) with atypical chest pain and negative exercise test, undergoing stress-redistribution thallium scan, served as controls. RESULTS: Exercise was discontinued for angina and/or ST-segment depression after 12 +/- 3 min. Thallium stress images revealed 40 hypoperfused segments in 27 patients (77%); after 4 h, 16 of these segments had completely normalized, 10 remained unchanged, six exhibited partial reperfusion and eight worsened. Twenty-four patients (69%) exhibited thallium reverse redistribution in 33 segments. Thirty-four patients (97%) had at least one hypoperfused segment in one of the two scintigraphic phases. Of the 24 patients with reverse redistribution, eight also underwent stress-rest 99m Tc-MIBI SPECT: six exhibited reduced tracer uptake that was present at rest, but not on stress images, in the same segments showing thallium reverse redistribution. Thallium stress images revealed four hypoperfused segments in three controls (9%); at redistribution, one segment normalized, two remained unchanged and one exhibited partial reperfusion. Additionally, there were four new underperfused segments appearing on redistribution in four patients (13%). Overall, there were seven controls (22%) with at least one hypoperfused myocardial segment in one of the two scintigraphic phases. CONCLUSIONS: Our study confirms that perfusion abnormalities are present in most syndrome X patients. Additionally, the data show that reverse redistribution (a perfusion defect that develops or becomes more evident on delayed imaging) is a common finding in these patients. The mechanisms of the phenomenon remain obscure: we suggest that it is due to inhomogeneous perfusion, and the hyperaemic response induced by exercise masks resting underperfusion of certain areas.

Adult↗
PubMed1996

Isolated left ventricular filling abnormalities may predict interleukin-2-induced cardiovascular toxicity.

Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration of high-dose IL-2 is limited by important cardiovascular side effects such as hypotension, fluid retention, arrhythmias, and myocardial ischemia, which often cause dose reduction and/or treatment withdrawal. The occurrence of these toxic events is not predicted by routine pretreatment examinations. The aim of the present study was to test the reliability of serial echocardiography in predicting subsequent cardiac adverse effects in patients undergoing IL-2 administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27-71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two-dimensional and Doppler echocardiography before and immediately after 28 continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for 4 days. Left ventricular systolic function and the diastolic transmitral flow pattern were assessed before and after IL-2 administration. Significant changes of two indexes of left ventricular filling were noted: a decrease of the ratio of maximal flow velocity in early diastole to that in late diastole (E/A) (basal: 1.12 +/- 0.46, mean +/- SD; posttreatment: 0.83 +/- 0.27; p < 0.01) and an increase of the percentage of the atrial contribution to left ventricular filling (basal: 37.75 +/- 11.58%; posttreatment: 49.43 +/- 16.48%; p < 0.01). Eight major cardiovascular events causing IL-2 infusion withdrawal were observed (two ischemic electrocardiographic modifications, three grade III-IV hypotension, one atrial fibrillation, one pericardial effusion, one acute heart failure). These major cardiovascular events were observed more often when an abnormal basal E/A ratio < 1.0 (p < 0.05) was found. We conclude that Doppler transmitral flow pattern analysis before and subsequent to IL-2 infusion is a useful and easily available procedure for the monitoring of cardiac modifications during CIVI IL-2 administration. It might also predict a major cardiovascular event during IL-2 administration. Patients with basal E/A ratio < 1.0 should be more carefully monitored during treatment and/or should be treated with lower IL-2 doses to avoid cardiovascular toxicity.

Adult↗
PubMed1996

Reverse perfusion pattern of Tc-99m MIBI heralding the development of myocardial infarction.

In a patient with sporadic atypical chest pain associated with dyspnea, stress Tc-99m MIBI imaging showed normal perfusion and inferoposterior hypoperfusion on the resting study. Although this reverse perfusion pattern was considered artifactual, the patient later had an acute myocardial infarction involving the same areas. Postinfarction stress Tc-99m MIBI imaging showed a nonreversible defect in the same area that, in the earlier study, showed a reverse perfusion pattern. The authors hypothesize that partial stenosis of the related artery with some nontransmural myocardial necrosis at the time of the initial study may be a possible cause of this peculiar Tc-99m MIBI perfusion pattern.

Aged↗
PubMed1995

Specificity and sensitivity of exercise-induced ST segment elevation for detection of residual viability: comparison with fluorodeoxyglucose and positron emission tomography.

OBJECTIVES: We evaluated the sensitivity and specificity of exercise-induced ST segment elevation for the detection of residual myocardial viability. BACKGROUND: Assessment of residual viability after myocardial infarction is relevant for establishing indication for revascularization. We have previously shown that exercise-induced ST segment elevation is a marker of residual viability. METHODS: We studied 34 patients with a previous Q wave myocardial infarction (anterior in 21, inferior in 13) of whom 18 (group A) had exercise-induced ST segment elevation in more than one lead (mean [+/- SD] 1.8 +/- 0.9 mm, range 1 to 4) and 16 (group B) did not. All patients underwent rest technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography (SPECT), fluorine-18 (F-18) fluorodeoxyglucose positron emission tomography and coronary angiography. The time elapsed between the infarction and the viability study was 72 +/- 108 days (range 15 to 400) in group A and 516 +/- 545 days (range 14 to 1,800) in group B. RESULTS: The presence and site of previous infarction were confirmed by SPECT studies in all 34 patients. Uptake of F-18 fluorodeoxyglucose within the infarcted area was present in 18 of 18 patients in group A but in only 9 (56%) of 16 in group B (p < 0.01). In patients with an anterior infarction, the sensitivity, specificity and predictive accuracy of exercise-induced ST segment elevation for detection of residual viability were 82%, 100% and 86%, respectively (95% confidence intervals 46% to 83.5%, 59% to 100% and 55.6% to 87.1%, respectively). CONCLUSIONS: Exercise-induced ST segment elevation in infarct-related leads has a high specificity and acceptable sensitivity for detection of residual viability within the infarcted area.

Coronary Angiography↗
PubMed1995

Fetal echocardiography in detecting anomalous pulmonary venous connection: four false positive cases.

Prenatal detection of congenital heart disease is possible from the 16th week of pregnancy, the ideal time being the mid-trimester, when most cardiac abnormalities can be detected. However, identification of anomalous pulmonary venous connection is difficult before birth and the sensitivity of fetal echocardiography in detecting this anomaly is low. Four cases are reported in which fetal echocardiographic findings obtained during the third trimester of pregnancy were highly suggestive of anomalous pulmonary venous connection. Right ventricular and atrial dominance associated with an enlarged coronary sinus or dilated superior vena cava were identified and considered to be indirect markers of the anomaly. No other cardiac anomaly was detectable. In all cases right ventricular and atrial dominance with dilated coronary sinus or superior vena cava were confirmed after birth despite the presence of normal pulmonary venous connections. These results confirm that the prenatal detection of this condition is difficult and should be based on the direct visualisation of anomalous pulmonary venous connections. The sole detection of indirect signs, such as right atrial and ventricular dominance with or without a dilated coronary sinus, superior vena cava, or inferior vena cava, does not warrant the diagnosis of anomalous pulmonary venous connection. Since the pulmonary venous flow in the human fetus is not as small as is commonly assumed, an anomalous drainage should be detectable when present and therefore should be specifically sought if the anomaly is suspected. The reasons for the presence of such transient cardiac anomalies remain obscure, but they might be related to functional or morphological rearrangement of the heart during fetal and perinatal life.

Echocardiography↗
PubMed1994

Antiischemic effects of intravenous diazepam in patients with coronary artery disease.

Diazepam (DZP) is commonly used in treatment of patients with acute ischemic syndromes to allay anxiety, but benzodiazepines reduce myocardial contractility and increase myocardial blood flow. To investigate the antiischemic effect of DZP, we studied 13 patients with a positive exercise test and angiographically documented coronary artery disease. All patients were submitted to a randomized, placebo-controlled trial using 0.9% NaCl infusion as placebo and intravenous (i.v.) diazepam (0.1 mg/kg in 20 min). Exercise tests performed immediately after the infusions showed that as compared with placebo, DZP significantly prolonged time to 1-mm ST-segment depression (557 +/- 198 vs. 428 +/- 226 s, p < 0.0001) and total exercise duration (624 +/- 177 vs. 561 +/- 188 s, p < 0.007). Rate-pressure product (RPP) at 1-mm ST-segment depression was not significantly different with the two treatments. DZP significantly delays onset of exercise-induced myocardial ischemia in patients with coronary artery disease. Because RPP at onset of ischemia was similar to that recorded with placebo despite greater levels of external workload, the antiischemic action of DZP appears to be mediated, at least partially, by a reduction in myocardial oxygen consumption.

Adult↗
PubMed1994

Impaired left ventricular filling rate induced by treatment with recombinant interleukin 2 for advanced cancer.

BACKGROUND: Immunotherapy with recombinant interleukin 2 (rIL 2) has been extensively used to treat cancer but its use has been hampered by serious side effects including severe hypotension, arrhythmias, and myocardial infarction. OBJECTIVE: To assess the effects of rIL 2 on human left ventricular function. METHODS: Left ventricular (LV) function was monitored in 22 patients (9 women, 13 men) (mean (SD) age 53 (10) years) undergoing a 120 h continuous intravenous infusion of rIL 2 (18 x 10(6) IU/m2/day) for melanoma (4), renal cell (16), ovarian (1), and colon cancer (1). Radionuclide ventriculography was performed before and 1 h after the end of treatment. Ejection fraction (EF), peak emptying rate (PER), peak filling rate (PFR), and regional left ventricular wall motion were analysed. Heart rate (HR), central venous pressure (CVP), systolic (SBP) and diastolic blood pressures (DBP), the electrocardiogram, and myocardial enzyme concentrations were monitored throughout the study. RESULTS: All variables (mean (SD)) were normal before rIL 2 was given. After rIL 2 administration HR increased significantly from 84 (11) to 125 (18) beats/min (p < 0.0001), SBP fell from 128 (11) to 100 (9) mmHg (p < 0.001) and DBP from 76 (9) to 65 (7) mmHg (p < 0.0001). CVP decreased from 3.70 (3.2) to 1.30 (0.45) cm H2O (p < 0.001). EF (65 (7) to 64 (8%) and PER (3.56 (0.60) to 3.86 (0.83) EDV/s) did not change significantly. PFR decreased significantly at the end of the rIL 2 infusion from 2.68 (0.46) to 2.37 (0.43) EDV/s (p < 0.01). Left ventricular segmental hypokinesia developed in 6 patients. Myocardial enzyme concentrations remained normal throughout the study. CONCLUSIONS: The results of this study confirmed that rIL 2 produces important haemodynamic changes, predominantly related to decreased systemic resistance. However, the observed reduction in PFR in most patients suggested that rIL 2 might exert its action at the level of the heart muscle itself. The localised systolic dysfunction in some patients suggested that rIL 2 might also adversely affect myocardial perfusion.

Blood Pressure↗