Assessment of coronary spasms with transluminal attenuation gradient in coronary computed tomography angiography.

PURPOSE: To evaluate the imaging features of coronary spasm, including transluminal attenuation gradient (TAG) on coronary computed tomography angiography (CCTA), in patients with vasospastic angina (VA). METHODS: A total of 43 patients with a high clinical likelihood of VA were included in the study. All the subjects underwent double CCTA acquisition: CCTA without a vasodilator ('baseline CT') and CCTA during continuous intravenous nitrate infusion ('IV nitrate CT'). A catheterized ergonovine provocation test was used to determine true VA patients. Coronary spasm is classified into focal- and diffuse-types according to morphological differences. We measured TAG and contrast enhancement of the proximal ostium (ProxHU) of each coronary artery for both the baseline and IV nitrate CT. RESULTS: Twenty-four patients (55.8%) showed positive results of coronary vasospasm on the provocation test. Thirty-eight vessels showed coronary spasms (29.5%): Focal-type in nine vessels (24%), and diffuse-type in 29 (76%). In the baseline CT, LCX showed significantly lower (steeper) TAG in spasm(+) vessels than in spasm(-) vessels, while LAD and RCA showed no significant differences in TAG. The ProxHU of LAD showed significantly lower values in spasm(+) vessels than in spasm(-) vessels, while the other vessels did not show significant differences in ProxHU. For IV nitrate CT, there were no significant differences in either the TAG and ProxHU between spasm(+) and (-) vessels for all the three vessel types. In subgroup analysis for spasm(+) vessels, diffuse spasms showed significantly lower TAG than focal spasms, while the ProxHU did not differ between the two types of spasm. CONCLUSIONS: A relatively large percentage of coronary spasms present as diffuse type, and the TAG values significantly differed according to the morphological type of the coronary spasm.

Uterotonic drugs to prevent postpartum haemorrhage: a network meta-analysis.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended. There are several uterotonic drugs for preventing PPH, but it is still debatable which drug or combination of drugs is the most effective. OBJECTIVES: To identify the most effective and cost-effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile. METHODS: The Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO)'s International Clinical Trials Registry Platform (ICTRP) were searched for unpublished trial reports (30 June 2015). In addition, reference lists of retrieved studies (updated October 2017) were searched for randomised trials evaluating uterotonic drugs for preventing PPH. The study estimated relative effects and rankings for preventing PPH, defined as blood loss of ≥ 500 ml and ≥ 1000 ml. Pairwise meta-analyses and network meta-analysis were performed to determine the relative effects and rankings of all available drugs and combinations thereof [ergometrine, misoprostol (Cytotec®; Pfizer Inc., New York, NY, USA), misoprostol plus oxytocin (Syntocinon®; Novartis International AG, Basel, Switzerland), carbetocin (Pabal®; Ferring Pharmaceuticals, Saint-Prex, Switzerland), ergometrine plus oxytocin (Syntometrine®; Alliance Pharma plc, Chippenham, UK), oxytocin, and a placebo or no treatment]. Primary outcomes were stratified according to the mode of birth, prior risk of PPH, health-care setting, drug dosage, regimen and route of drug administration. Sensitivity analyses were performed according to study quality and funding source, among others. A model-based economic evaluation compared the relative cost-effectiveness separately for vaginal births and caesareans with or without including side effects. RESULTS: From 137 randomised trials and 87,466 women, ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin were found to reduce the risk of PPH blood loss of ≥ 500 ml compared with the standard drug, oxytocin [ergometrine plus oxytocin: risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83; carbetocin: RR 0.72, 95% CI 0.52 to 1.00; misoprostol plus oxytocin: RR 0.73, 95% CI 0.6 to 0.9]. Each of these three strategies had 100% cumulative probability of being ranked first, second or third most effective. Oxytocin was ranked fourth, with an almost 0% cumulative probability of being ranked in the top three. Similar rankings were noted for the reduction of PPH blood loss of ≥ 1000 ml (ergometrine plus oxytocin: RR 0.77, 95% CI 0.61 to 0.95; carbetocin: RR 0.70, 95% CI 0.38 to 1.28; misoprostol plus oxytocin: RR 0.90, 95% CI 0.72 to 1.14), and most secondary outcomes. Ergometrine plus oxytocin and misoprostol plus oxytocin had the poorest ranking for side effects. Carbetocin had a favourable side-effect profile, which was similar to oxytocin. However, the analysis was restricted to high-quality studies, carbetocin lost its ranking and was comparable to oxytocin. The relative cost-effectiveness of the alternative strategies is inconclusive, and the results are affected by both the uncertainty and inconsistency in the data reported on adverse events. For vaginal delivery, when assuming no adverse events, ergometrine plus oxytocin is less costly and more effective than all strategies except carbetocin. The strategy of carbetocin is both more effective and more costly than all other strategies. When taking adverse events into consideration, all prevention strategies, except oxytocin, are more costly and less effective than carbetocin. For delivery by caesarean section, with and without adverse events, the relative cost-effectiveness is different, again because of the uncertainty in the available data. LIMITATIONS: There was considerable uncertainty in findings within the planned subgroup analyses, and subgroup effects cannot be ruled out. CONCLUSIONS: Ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are more effective uterotonic drug strategies for preventing PPH than the current standard, oxytocin. Ergometrine plus oxytocin and misoprostol plus oxytocin cause significant side effects. Carbetocin has a favourable side-effect profile, which was similar to oxytocin. However, most carbetocin trials are small and of poor quality. There is a need for a large high-quality trial comparing carbetocin with oxytocin; such a trial is currently being conducted by the WHO. The relative cost-effectiveness is inconclusive, and results are affected by uncertainty and inconsistency in adverse events data. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015020005; Cochrane Pregnancy and Childbirth Group (substudy) reference number 0871; PROSPERO-Cochrane (substudy) reference number CRD42015026568; and sponsor reference number ERN_13-1414 (University of Birmingham, Birmingham, UK). FUNDING: Funding for this study was provided by the National Institute for Health Research Health Technology Assessment programme in a research award to the University of Birmingham and supported by the UK charity Ammalife (UK-registered charity 1120236). The funders of the study had no role in study design, data collection, data synthesis, interpretation or writing of the report.

Postpartum haemorrhage (PPH) is the most common reason why mothers die in childbirth worldwide. Although most healthy women can cope well with blood loss after birth, some do not, and this can pose a serious risk to their health and even life. To reduce blood loss after birth, the routine administration of a drug to contract the uterus (uterotonic) has become standard practice across the world. This research seeks to identify which is the most effective and cost-effective drug. Different drugs have been used for reducing the occurrence of PPH. They include oxytocin, misoprostol, ergometrine, carbetocin, and combinations of these drugs, each with different effectiveness and side effects. The study synthesised the available evidence to compare all of these drugs and combinations thereof. After putting the results of all available comparisons together in a network, a ranking among them was calculated, and provided robust effectiveness and side-effect profiles for each drug and their associated costs. The study included 137 randomised trials, involving a total of 87,466 women. The results suggested that ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are the most effective strategies for preventing PPH and are more effective than the currently recommended drug, oxytocin. Each of these three strategies had almost 100% probability of being ranked first, second or third most effective. Oxytocin was ranked fourth with an almost 0% probability of being ranked in the top three. Ergometrine plus oxytocin and misoprostol plus oxytocin were the worst drug combinations for side effects, with carbetocin having the most favourable side-effect profile. Carbetocin could prevent approximately one further event of PPH out of three in comparison with oxytocin. However, existing carbetocin studies were small and of poor quality. There is need for a large high-quality study comparing carbetocin with the current standard treatment of oxytocin for the prevention of PPH. The cost analyses of the alternative drug strategies remain inconclusive.

Intramuscular oxytocin versus oxytocin/ergometrine versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: study protocol for a randomised controlled trial (the IMox study).

BACKGROUND: Postpartum haemorrhage remains a major cause of maternal mortality and morbidity worldwide. Active management of the third stage of labour reduces the risk of postpartum haemorrhage. Oxytocin and oxytocin/ergometrine are commonly used in the UK, with oxytocin/ergometrine being more effective at preventing moderate, but not severe, blood loss. Many guidelines specifically recommend using oxytocin for all vaginal births, as it is associated with fewer adverse events. However, a survey conducted by the Southmead Hospital Maternity Research Team revealed that 71.4% of UK obstetric units still routinely use oxytocin/ergometrine. Carbetocin is a newer medication that may be as effective but has fewer side effects. No studies have directly compared all three medications. METHODS: The IMox study aims to determine the most effective, acceptable and cost-effective drug for primary prevention of postpartum haemorrhage following vaginal birth. The IMox study is a prospective, multi-centre, double-blind, randomised trial directly comparing oxytocin, oxytocin/ergometrine and carbetocin given intramuscularly for the prevention of postpartum haemorrhage in the third stage of labour. The primary effectiveness outcome is the use of an additional uterotonic drug. Secondary effectiveness outcomes reflect maternal morbidity and mortality within the immediate postpartum period. Participant questionnaires and subjective reporting of side effects will be used to evaluate maternal acceptability. Maternal quality of life utilities will be collected antenatally, and on days 1 and 14 after birth to enable a cost-effectiveness assessment of each studied drug. Participants will be pregnant women planning a vaginal birth in six hospitals in England. Participants will be approached and invited to provide consent to participate from 20 weeks gestation until in established labour. A complete sample of 5712 participants (1904 per arm) providing data for the primary outcome will allow for a robust determination of efficacy between all three study drugs. Data will be collected until participants are discharged from the hospital and on postnatal days 1 and 14 regardless of location. All analyses will be on a modified intention-to-treat basis, and additionally repeated on a per protocol basis. Data collection commenced in Feburary 2015 and was completed in August 2018. DISCUSSION: This study is the first to directly compare oxytocin, oxytocin/ergometrine and carbetocin in the same population for the prevention of postpartum haemorrhage following vaginal birth. Furthermore, this study will be the first to directly compute health economic outcomes from such a three-way comparison. This study is limited to using short-term outcomes, and so will not provide evidence for important outcomes such as long-term maternal psychological well-being and time to next conception. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02216383 . Registered on 18 August 2014. EudraCT, 2014-001948-37. Registered on 23 September 2014. ISRCTN, ISRCTN10232550. Retrospectively registered on 6 March 2018).

The Quality of Selected Essential Medicines Sold in Accredited Drug Dispensing Outlets and Pharmacies in Tanzania.

INTRODUCTION: The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. METHODS: We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia's monograph for artemether-lumefantrine. RESULTS AND DISCUSSION: The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to poor distribution and storage rather than poor manufacturing practices. CONCLUSIONS: Over 90% of the medicines sold in ADDOs and pharmacies met quality standards. Policy makers need to reconsider ergometrine maleate's place on the list of medicines that ADDOs are allowed to dispense, by either substituting a more temperature-stable therapeutically equivalent product or requiring those sites to have refrigerators, which is not a feasible option for rural Tanzania.

A systematic assessment of the variability of matrix effects in LC-MS/MS analysis of ergot alkaloids in cereals and evaluation of method robustness.

The study presents for the first time a systematic investigation of matrix effects in the LC-MS/MS analysis of ergot alkaloids in cereals. In order to assure the accuracy of the results, several approaches to minimize/eliminate matrix effects were investigated including variation of ionization techniques, chromatography and sample preparation on different grain types and grain varieties. It was revealed that the use of UPLC and careful choice of sample preparation might reduce signal suppression/enhancement. In general, ergometrine was found to be the most susceptible among the ergot alkaloids studied, but none of the used approaches suggested a total elimination of matrix effects; only less than half of its MS signal could be recovered. The late-eluting compounds were less affected by matrix components in all conditions tested. Further, the robustness of the applied LC-MS method was checked by means of a fractional factorial design. The results indicate that small changes to the sample preparation parameters, namely pH and concentration of extraction buffer, shaking time, drying temperature and extraction volumes, did not significantly (α = 0.05) affect the recoveries of ergot alkaloids.

In vivo assessment of ergonovine-induced coronary artery spasm by 64-slice multislice computed tomography.

BACKGROUND: The potential of multislice CT (MSCT) to predict coronary spasm has not been elucidated. The aim of this study was to investigate whether the morphological features observed on MSCT at the site of ergonovine-induced epicardial spasm could be used as diagnostic criteria for coronary spasm. METHODS AND RESULTS: A total of 296 plaques in 199 patients with clinically suspected coronary spastic angina without coronary stenosis (<75%) who underwent invasive angiography with intravenous ergonovine provocative testing were analyzed by MSCT. Calcification, CT attenuation, and patterns of vascular remodeling were evaluated in each plaque by MSCT. Plaques were divided into spasm group or nonspasm group based on the results of the ergonovine provocative test. On a per-plaque basis, noncalcified plaques were more frequently observed in the spasm group (96% versus 20%, P<0.01). Intermediate attenuation plaques (CT density ≥53.8 Hounsfield units identified by receiver operating characteristic analysis) were more common in the spasm group (93% versus 28%, P<0.01), as was negative remodeling (67% versus 11%, P<0.01). Multivariable analysis revealed noncalcified (odds ratio [OR], 48.7; 95% CI, 8.81-269; P<0.01), intermediate attenuation (OR, 19.3; 95% CI, 4.96-75.4; P<0.01); negative remodeling (OR, 8.83; 95% CI, 2.87-27.2; P<0.01); and male sex (OR, 4.55; 95% CI, 1.24-16.6; P=0.02) as predictors of the plaque associated with coronary spasm. CONCLUSIONS: MSCT can detect differences in individual plaque composition and morphology among atherosclerotic plaques without significant luminal narrowing in areas of inducible vasospasm compared to areas without vasospasm.

Coronary vasospastic angina: assessment by multidetector CT coronary angiography.

OBJECTIVE: We aimed to describe the imaging findings of multidetector CT coronary angiography (MDCTA) in cases of vasospastic angina (VA) and to determine the accuracy of MDCTA in the identification of VA as compared with invasive coronary angiography with an ergonovine provocation test (CAG with an EG test). MATERIALS AND METHODS: Fifty-three patients with clinically suspected VA were enrolled in this study. Two radiologists analyzed the stenosis degree, presence or absence of plaque, plaque composition, and a remodeling index of the related-segment in CAG with an EG test, which were used as a gold standard. We evaluated the diagnostic performances of MDCTA by comparing the MDCTA findings with those of CAG with an EG test. RESULTS: Among the 25 patients with positive CAG with an EG test, all 12 patients with significant stenosis showed no definite plaque with the negative arterial remodeling. Of the six patients with insignificant stenosis, three (50%) had non-calcified plaque (NCP), two (33%) had mixed plaque, and one (17%) had calcified plaque. When the criteria for significant stenosis with negative remodeling but no definite evidence of plaque as a characteristic finding of MDCTA were used, results showed sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) of 48%, 100%, 100%, and 68%, respectively. CONCLUSION: Significant stenosis with negative remodeling, but no definite evidence of plaque, is the characteristic finding on MDCTA of VA. Cardiac MDCTA shows good diagnostic performance with high specificity and PPV as compared with CAG with an EG test.

Assessment of coronary conductance and resistance vessel reactivity in response to nitroglycerin, ergonovine and adenosine: in vivo studies with simultaneous intravascular two-dimensional and Doppler ultrasound.

OBJECTIVES: The aim of this study was to determine the differential effects of nitroglycerin, ergonovine and adenosine on the resistance vessels in vivo by using a Doppler-tipped guide wire in combination with an ultrasound imaging catheter. BACKGROUND: Catheter-based two-dimensional intravascular ultrasound yields images of the coronary arteries from which cross-sectional areas can be measured. Intravascular Doppler ultrasound techniques allow measurement of coronary blood flow velocity. The simultaneous use of the two techniques can yield anatomic and physiologic information on conductance and resistance vessels but has not been tried in the coronary arteries. METHODS: In 15 dogs, we studied coronary flow and vascular reactivity in response to pharmacologic agents using two approaches: 1) a 30-MHz, 4.3F imaging catheter placed alongside a 0.018-in. (0.046 cm) Doppler wire in the circumflex or left anterior descending coronary artery (n = 5); 2) the ultrasound imaging catheter introduced directly over a 0.014-in. (0.036 cm) Doppler wire (n = 10). Vasodilator and vasoconstrictor responses were studied by using intracoronary nitroglycerin (50, 100 and 200 micrograms), ergonovine (200 micrograms) and adenosine (6 mg). RESULTS: Nitroglycerin caused a dose-dependent increase in epicardial coronary artery cross-sectional area and, to a lesser extent, in average peak flow velocity, resulting in an increase in volumetric coronary blood flow of 39% and 50% at the doses of 100 and 200 micrograms, respectively. With these doses of nitroglycerin, the decrease in diastolic to systolic velocity ratio and the increased change in cross-sectional area from end-diastole to end-systole suggested an enhanced epicardial coronary artery compliance. With ergonovine, a 12% reduction in epicardial coronary artery cross-sectional area was seen, without a significant change in average peak velocity, resulting in a 15% decrease in volumetric coronary blood flow. Adenosine caused a 270% increase in average peak velocity but no change in epicardial coronary artery cross-sectional area, resulting in a 270% increase in volumetric blood flow. CONCLUSIONS: This study demonstrates that nitroglycerin and ergonovine predominantly influence coronary conductance arteries whereas adenosine mainly dilates coronary resistance vessels. These findings also demonstrate that the combined use of a two-dimensional and a Doppler ultrasound transducer within one catheter assembly can provide information on the differential effects of vasoactive agents on the epicardial and microvascular coronary circulation.

[Prescribing of ergometrine for abortion without physical examination]. / Voorschrijven van ergometrine wegens abortus zonder onderzoek.

PIP: The report of the Board of Medical Discipline in the Hague considering a case in which the complainant is a woman who went to the toilet in her 11th week of pregnancy, heard a splash and began to hemorrhage. The complainant called the defendant physician and requested an immediate visit. The physician found that a visit was not necessary and gave a telephone diagnosis of a miscarriage and prescribed ergometrine (Ermitrine) 1 tablet 3 X daily. About an hour later the complainant became sick and was admitted to the hospital with what turned out to be an incomplete gemelli miscarriage. The complainant held that the physician was negligent on 2 occasions, 1st during the telephone conversation; 2d when the complainant picked up the prescription from the physician, in that he made a diagnosis without a physical examination and prescribed ergometrine. The board ruled that the physician should have determined by means of a vaginal examination whether the abortion had been complete. He was also in error in prescribing ergometrine since this always causes contraction of the uterus and this action is not indicated if there are remnants still in the uterus. By failing to make an examination before prescribing ergometrine the physician was guilty of an action which undermined confidence in medicine. The board voted to issue a letter of caution to the physician and directed that the case be registered with the Ministry of Welfare, Public Health and Culture and published in the medical journals.^ieng

Value of noninvasive assessment of patients with atypical chest pain and suspected coronary spasm using ergonovine infusion and thallium-201 scintigraphy.

Twenty-six patients with known benign coronary anatomic characteristics and atypical chest pain syndromes were evaluated for the possibility of coronary spasm. Incremental intravenous ergonovine maleate infusions were administered, and thallium-201 scintigraphy was performed at the peak dosage and during recovery in the coronary care unit. With ergonovine therapy, 4 patients (16%) had chest pain associated with electrocardiographic (ECG) or scintigraphic changes. Nine patients (35%) had chest pain without associated ECG or scintigraphic changes, and 13 patients did not have chest pain in response to ergonovine administration, although 2 (8%) had ergonovine-induced scintigraphic defects. All 4 patients with ergonovine-induced chest pain and associated ECG or scintigraphic abnormalities had resolution or reduction of chest pain after medical treatment. However, 7 of the 9 patients with ergonovine-induced chest pain in the absence of ECG or scintigraphic abnormalities continued to have symptoms despite medical treatment a mean of 18 months later. In this limited study of a select group, bedside ergonovine provocation appeared safe. Many patients had chest pain, but few showed ECG or scintigraphic evidence of ischemia. Perfusion scintigraphy appears to have potential complementary value for the identification of an ischemic cardiac cause of atypical chest pain and provides a rationale for appropriate therapy.

[Clinical assessment of coronary vascular stiffness and tone by pressure-diameter relationships of the coronary arteries].

To assess the elastic properties of the human coronary arteries, we investigated dynamic pressure-diameter relationship (P-D loop) of the left main coronary artery (LMCA) using cine coronary arteriography (CAG). Intracoronary pressures were ascertained using a high-fidelity manometer placed in the sinus of Valsalva, and the caliber of the coronary artery was measured from the magnified (4-inch image intensifier) CAG using a computerized image processing technique. The dynamic incremental elastic moduli (Ep = (delta P/delta D) X D, delta P: pulse pressure, delta D: change in coronary diameter in a cardiac cycle, D: mean diameter) were calculated from P-D loops of the coronary arteries for assessing their elastic properties. To test the hypothesis that coronary arterial wall stiffness increases with age and/or arteriosclerosis involvement, the coronary arterial elastic properties (Ep) of the LMCA were studied in normal subjects ranging widely in age (41 to 68 years of age) and in patients with coronary artery disease but without narrowing of their LMCAs. Furthermore, to assess the effects of coronary vasoactive agents, nitroglycerin (NG) and ergonovine maleate (EM), on coronary vascular tone, a shift of the P-D loops and a change in the Ep were also studied. The study population consisted of 40 patients who underwent CAG because of chest pain and abnormal ECG. Thirty-four patients without angina at rest were categorized in three groups (G) according to CAG findings; G-1: 15 normal subjects, G-2: eight patients with single vessel disease, G-3: 11 patients with multi-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of sublingual isosorbide dinitrate and intracoronary nifedipine during ergonovine provocation.

In 37 patients with suspected vasospastic angina diagnostic ergonovine testing was used as a method of analysing the efficacy of sublingual ISDN in comparison with sublingual and intracoronary nifedipine on coronary luminal diameter, left ventricular ejection fraction, aortic blood pressure, heart rate and left ventricular end-diastolic pressure. 10 mg of sublingual ISDN counteracted the ergonovine effects on left ventricular pump function and hemodynamics. The luminal diameter of the epicardial coronary arteries increased from 3.5 +/- 0.8 to 4.9 +/- 0.8 mm. 20 mg of sublingual nifedipine did not change the coronary luminal diameter within 8-10 minutes after the ergonovine test. After administration of 0.1 mg of nifedipine into the right and left coronary artery the luminal diameters increased in the same range as after sublingual ISDN. Whereas the aortic blood pressure decreased after intracoronary nifedipine from 170 +/- 23 to 153 +/- 27 mmHg with a concomitant increase in heart rate, no effect on the left ventricular pump function could be assessed. In the model of ergonovine testing ISDN has shown itself as a potent drug in releasing the ergonovine effects. Sublingual ISDN is as potent as intracoronary nifedipine in releasing the ergonovine-induced reduction of coronary luminal diameters and more potent in counteracting the ergonovine effects concerning the cardiac pump function.