Cardiotropic Activity Research Articles

Preclinical Evaluation of hydroalcoholic extract of Moringa oleifera leaves for its Cardiotropic activity on albino Wistar rat

Object Moringa oleifera has numerous medicinal values and uses worldwide. Moringa oleifera is applied to remedy numerous diseases like malaria, arthritis, parasitic diseases, typhoid fever, swelling, cuts, and diseases of the skin, diabetes, and hypertension. However, no scientific evidence is available about the cardio-tropic activity of Moringa oleifera. The current research was carried out to investigate the cardio-tropic activity of hydro-alcoholic extract of Moringa oleifera leaves on the isolated heart of the Albino Wistar rat. The Moringa oleifera leaves were collected, washed, shade dried, and extracted with 70% ethanol. A stock solution (100µg/ml) was prepared by using distilled water. The cardio-tropic activity was screened on the isolated rat heart at a dose of 0.1ml, 0.2ml, and 0.4ml of 70% ethanolic extract of the Moringa oleifera leaf. Acetylcholine (0.0125ml, 0.0250ml, 0.0500ml, 0.1000ml) and adrenaline (0.05ml, 0.1ml, 0.2ml, 0.4ml) were used as standard drugs. Also, on the isolated rat heart, the dose-response curve of 70% ethanolic extract of the Moringa oleifera leaf and the standard drugs were screened at the above same dose. The 70% ethanolic extract of Moringa oleifera leaf (100µg/ml) has produced significant negative cardio-tropic activity as compared to standard drugs. The study indicates that 70% ethanolic extract of Moringa oleifera leaf shows substantial negative cardio-tropic activity on the isolated rat heart in dose dependent manner.

Chemical composition and cardiotropic activity of Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f.

Ethnopharmacological relevanceZiziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is a subshrub that is widely distributed in China, Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, and Uzbekistan. The species is used in traditional medicine for the relief of symptoms connected to cardiovascular diseases like coronary heart disease or hypertension. Aim of the studywas to validate traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary hearth diseases using in vivo models and to find active compounds responsible for the activity. Materials and methodsMultiple extracts were obtained from the aerial parts of Z. clinopodioides subsp. bungeana using maceration, liquid-liquid extraction, CO2 extraction and ultrasound-assisted extraction. Preliminary screening studies for the evaluation of the efficacy of Z. clinopodioides subsp. bungeana extracts on the model of hemic hypoxia were performed. The most effective samples were selected and included in the main study. Stage 2 of the study evaluated the cardiotropic activity of the selected extracts on a model of chronic heart failure. Preparations were administered to animals intragastrically once a day for 28 days. For the isolation of individual compounds plant material was extracted with 96% ethanol. The obtained crude extract was sequentially extracted with n-hexane and dichloromethane and separated by chromatography on a Diaion HP-20 column. The obtained fractions were further subjected to Sephadex LH-20 column chromatography and eluted isocratically with 96% ethanol (EtOH) to yield subfractions, which were further separated by preparative HPLC to obtain 13 individual compounds. ResultsExtracts obtained from Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. herb were subjected to pharmacological screening for the evaluation of their efficacy on hemic hypoxia. Based on the obtained results, out of the sixteen tested extracts two (AR and US 60%) were selected for further evaluation of their cardiotropic activity. Modeling of chronic heart failure was carried out in accordance with the following stages: 1) anesthesia with chloral hydrate at a dose of 450 mg/kg, intraperitoneally, 2) artificial ventilation of the lungs, 3) thoracotomy, 4) modeling of permanent ischemic or ischemic-reperfusion damage. Both extracts effected the indicators of contraction and output, comparable to the reference drug - Monopril. Based on the extraction methods used to obtain RAF and US60 and data from the literature, it can be assumed that they contain compounds with medium polarity, including polyphenols and terpenoids. At the next stage three previously undescribed monoterpenoid derivatives – Ziziphoric acid (1), Ziziphoroside D (2) and 6′-malonylziziphoroside A (3), along with two previously described megastigmane glucosides – blumenol C glucoside (4), blumenol C 9-O-(6′-O-malonyl-beta-D-glucopyranoside (5) and two previously described monoterpenoids 7a-hydroxymintlactone (6), 7-hydroxypiperitone (7) together with six polyphenols – pinocembrine-7-O-rutinoside (8), chrysine-7-O-rutinoside (9), acacetin-7-O-rutinoside (10), luteolin-7-O-rutinoside (11), rutin (12) and rosmarinic acid (13) were isolated from Z. clinopodioides subsp. bungeana extracts. ConclusionOur results support the traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary diseases. As a result of Z. clinopodioides subsp. bungeana extracts screening in vivo, two extracts were selected as potential cardiotropic agents. Phytochemical analysis of the plant material led to the isolation of five terpenoid derivatives, two megastigmane glycosides, five flavonoids and one cinnamic acid derivative, which could be responsible for the reported biological activity. Future experiments are required to understand the mechanisms of action for the isolated compounds.

Changes in micro- and central hemodynamic parameters in rats under the action of acetylsalicylic acid and its coordination compounds with metals

Introduction. The cutaneous blood circulation is a representative model both for studying the mechanisms of vascular diseases and for assessing the current state of the central hemodynamics in preclinical researches of various chemical compounds. Aim. The changes in the parameters of cutaneous microcirculation and central hemodynamics (heart rate and blood pressure) were studied in the animals under the action of acetylsalicylic acid and its coordination compounds with cations of cobalt, zinc, nickel and manganese at a dose of 20 mg/kg. Materials and methods. The research was conducted using the laser Doppler flowmetry method on the Lazma-MC device (manufactured by RPE Lazma, Russia) and the NIBP200A system (Biopac Systems, Inc., USA). Results. The study shows that animals develop bradycardia, and microcirculation and central hemodynamics change in two ways after the introduction of acetylsalicylic acid and the tested metal salicylates. These ways are hypotension-related hyperemia (acetylsalicylic acid and cobalt salicylate) and ischemia (zinc, nickel and manganese salicylates) associated with hypertension. Conclusion. The obtained data confirm the cardiotropic activity of new coordination compounds. The data also prove that the generation of the acetylsalicylic acid derivatives allows enhancing it physiological effects, as well as obtaining completely new molecules. The molecules are different from the precursor one and are necessary for the production of effective drugs.

Synthesis and Cardiotropic Activity of bis-(2,3,4-Trimethoxybenzyl)Alkanediamines

Synthesis and Cardiotropic Activity of bis-(2,3,4-Trimethoxybenzyl)Alkanediamines

INFLUENCE OF ATP-LONG AND MOLSIDOMINE COMBINATION ON THE BIOELECTRIC ACTIVITY OF THE MYOCARDIAL OF YOUNG AND OLD RATS IN CHRONIC SOFT STRESS

Introduction. Age-related changes in the cardiovascular system lead to a decrease in its reserve adaptive capabilities and an increase in the likelihood of developing diseases under stress and overstrain. A number of experiments have proven the significant role of emotional overstrain and stress in the development of cardiovascular diseases. The high incidence of the circulatory system, the long course and severity of diseases in elderly and old people determine the relevance of the search for treatment using effective and safe drugs. Aim: iinvestigate the effect of a combination of ATP-LONG and molsidomine on the functional state of the myocardium of young and old rats under chronic soft stress. Materials and methods. In experiments on young (10 months) and old (24 months) male Wistar rats, the cardiotropic and cardioprotective activity of the combination of the metabolic cardioprotector ATP-LONG and the vasodilator molsidomine was studied under conditions of chronic soft stress. Results. The negative impact of chronic soft stress on the bioelectrical activity of the myocardium – a violation of the processes of repolarization, conduction and contractility of the heart was found in young rats. The combination of ATP-LONG and molsidomine normalized the bioelectrical activity of the myocardium and increased its resistance to stress factors. In old rats under the influence of chronic stress, signs of impaired repolarization and electrical instability of the heart were more significant than in young animals. The combination ATP-LONG and molsidomine prevented the damaging effect of chronic stress and contributed to the normalization of the electrophysiological parameters of the myocardium of old rats. Conclusions. The results of experiments indicate the pharmacological cardiotropic activity of the combination of ATPLONG and molsidomine in young and old rats with chronic soft stress. Keywords: young rats, old rats, chronic soft stress, myocardium, electrocardiogram, bioelectrical activity of the heart, ATP-LONG, molsidomine, cardioprotective effect.

Experimental Evaluation of Anxiolytic and Analgesic Properties of a New Linear Methoxyphenyltriazaalkane Derivative with Cardiotropic Activity.

The anxiolytic and analgesic properties of compound ALM-802, a cardiotropic linear methoxyphenyltriazaalkane derivative, combining pharmacophore elements of p-FOX inhibitors trimetazidine and ranolazine were studied in vivo. In the elevated plus-maze test, ALM-802 after acute intraperitoneal administration in doses of 1-8 mg/kg dose-dependently prevented the development of anxiety in BALB/c mice. Chronic intraperitoneal administration of ALM-802 in a dose of 2 mg/kg to alcohol-preferring rats attenuated anxiogenesis induced by ethanol withdrawal. ALM-802 demonstrated antinociceptive activity in C57BL/6 mice during thermal stimulation of nociceptors in the hot plate test and during modeling of visceral pain in the acetic acid writhing test. Thus, ALM-802 exhibits anxiolytic and analgesic properties in the dose range corresponding to its anti-ischemic and antiarrhythmic effects.

Influence of Aromatic-Group Structure on Cardiotropic Activity of Alkoxyphenyltriazaalkanes

Previously, ALM-802 (N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine trihydrochloride) and ALM-803 (N1-(3,4,5-trimethoxybenzyl)-N2-{2-[(3,4,5-trimethoxybenzyl) amino]ethyl}-1,2-ethanediamine trihydrochloride), which combined pharmacophores of the free fatty-acid oxidation inhibitors trimetazidine and ranolazine and the slow Ca2+-channel blocker verapamil, were synthesized by us. These compounds possessed anti-ischemic and antiarrhythmic activities. Herein, the new compound ALM-843 (N1-(3,4-dimethoxybenzyl)-N2-{2-[(3,4-dimethoxybenzyl)amino]ethyl}-1,2-ethanediamine trihydrochloride), which exhibited only antiarrhythmic activity, was prepared. The results led to the hypothesis that the antiarrhythmic activity of the linear alkoxyphenyltriazaalkanes was due to the presence of a 3,4-dimethoxyphenyl pharmacophore, which is also present in verapamil. This hypothesis was confirmed using molecular docking to show that the above alkoxyphenyltriazaalkanes bound similarly to the verapamil binding site of the voltage-gated Ca2+-channel.

Экспериментальная оценка анксиолитических и анальгетических свойств нового производного линейных метоксифенилтриазаалканов с кардиотропной активностью

Экспериментальная оценка анксиолитических и анальгетических свойств нового производного линейных метоксифенилтриазаалканов с кардиотропной активностью

Search for angiotensin II receptor antagonists among 4-aryl-n-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine derivatives

The aim of study was to find potential antihypertensive and cardiotropic drugs among new 4-aryl-N-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imines. Materials and methods: The target compounds were synthesized by condensation asymmetrical substituted thioureas with α-bromo-4-R1-acetophenones in ethanol medium. The structure and purity of the compounds synthesized were confirmed by 1H, 13C NMR-spectroscopy and elemental analysis. Docking studies of synthesized compounds to the active site of angiotensin receptor ІІ (PDB ID: 3R8A) were performed in order to find its potential inhibitors and to select promising compounds for experimental screening. Pharmacological studies of the influence on the cardiovascular system were performed. Results: The results of docking studies indicate a high affinity of all tested substances to the selected biotarget. The thermodynamic probability of binding of synthesized substances to protein 3R8A was confirmed by negative values of scoring functions. Hydrobromide of 4-(4-methoxyphenyl)-N-phenyl-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine 3(1) and hydrobrmide of 4-(4-methoxyphenyl)-N-(4-bromphenyl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine 3(3), which have the highest negative values of scoring functions, are recommended for in vivo pharmacological studies. Based on a complete analysis of the geometric location of the synthesized compounds (ligands) in the active site of the angiotensin II receptor, it was found that the complexes are formed with the involvement of Nitrogen atom of imino group, the 1,3-thiazole ring, the phenyl and alkyl moieties of the molecule form hydrogen bonds, intermolecular electrostatic and donor-acceptor interactions. The conducted pharmacological studies of the influence on the cardiovascular system have allowed to confirm the presence of antihypertensive effect inherent in compounds of this series (except for compound 3(2)). The most effective antihypertensive effect, which is similar in duration and strength of the effect of valsartan, was the effect of compound 3(5). Conclusions: In order to expand the arsenal of biologically active substances of cardiotropic action a systematic series of new 4-aryl-N-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine derivatives were synthesized. The structure and purity of the compounds synthesized were confirmed by 1H, 13C NMR-spectroscopy and elemental analysis. Based on the results of docking studies using Autodock 4.2.6 software, selected compounds with the best affinity for protein biomes (PDB codes: 3R8A) are promising for experimental studies of hypotensive and cardiotropic activity. The most effective antihypertensive effect, which is similar in duration and strength of the effect of valsartan, was the effect of compound 3(5). A comparative analysis of the results of molecular docking and in vivo results suggests that there is a positive correlation between scoring protein inhibition and experimental data.

Synthesis and Cardiotropic Activity of 1-(Methoxybenzyl)-4-{2-[(Methoxybenzyl)-Amino]Ethyl}Piperazines

A group of new 1-(methoxybenzyl)-4-{2-[(methoxybenzyl)amino]ethyl}piperazines (1) were synthesized. The relationship of the structure of the triazaalkane linker and the cardiotropic activity in a series of these compounds was compared with that of previously studied linear and cyclic methoxyphenyltriazaalkanes. The most active compound in the group was 1e (1-(3,4,5-trimethoxybenzyl)-4-{2-[(3,4,5-trimethoxybenzyl)amino] ethyl}piperazine trihydrochloride) with statistically significant antiarrhythmic activity in aconitine and CaCl2 arrhythmia models.

Synthesis and Cardiotropic Activity of Cyclic Methoxyphenyltriazaalkanes

Synthesis and Cardiotropic Activity of Cyclic Methoxyphenyltriazaalkanes

Synthesis and Cardiotropic Activity of Linear Methoxyphenyltriazaalkanes

A new group of potential pFOX inhibitors among linear methoxyphenyltriazaalkanes were designed and synthesized. Cardiotropic activity in rodent experiments was found for most of the synthesized compounds. The most active compound N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine trihydrochloride (LM-1) combined anti-ischemic, antiarrhythmic, and antifibrillatory activities (1 mg/kg, i.v.) and low toxicity (LD50 = 119 mg/kg, mice, i.p.) and was selected for development as a potential cardiotropic drug.

Delayed Results of Experimental Afobazole Therapy in Rats after Acute Myocardial Infarction.

Delayed cardioprotective effects of anxiolytic Afobazole (15 mg/kg, intraperitoneally for 14 days) were evaluated using dynamic echocardiographic recordings on days 2, 15, 56, and 98 after experimental myocardial infarction modeling (rat model of acute myocardial ischemia). The cardiotropic activity of Afobazole is assumed to be related to its agonistic effects on σ1 receptor of cardiomyocytes. It was found that animals treated with Afobazole had no signs of heart failure by the end of observation, as evidenced by left ventricular ejection fraction.

DCMP AS A CLINICAL SYNDROME: RESULTS OF NOSOLOGICAL DIAGNOSTICS WITH MYOCARDIAL BIOPSY AND DIFFERENTIATED TREATMENT IN VIRUS-POSITIVE AND VIRUS-NEGATIVE PATIENTS

Aim. The nosological diagnostics in patients with the baseline syndromic diagnosis “dilated cardiomyopathy” (DCMP) with the use of myocardial biopsy and evaluation of complex treatment (cardiotropic, antiviral, immune suppressing, surgical), including virus-positive and virus-negative patients with myocarditis. Material and methods . Totally, 220 patients included with DCMP syndrome, 69 women and 151 men (31,4% and 68,6%), from 16 to 77 y. o. (mean age — 47,5±12,5,) with dilation and systolic dysfunction of the left ventricle (LV); end diastolic size (EDS) more than 5,5 cm; ejection fraction (EF) less than 50%, and absence of exclusion criteria. Mean EDS was 6,5 [6,0; 7,1] cm, EF — 30,3±10,1%, dp/dt 659 [535; 774,25] mmHg, VTI — 10,8±3,9 cm. The assessments were done of the anticardial antibodies via immune enzyme assay (IEA) and PCR-diagnostics of viral genome in blood of 95,5% patients, tread-mill test (5,9%), coronary arteriography (41,8%), MSCT (67,7%), MRI (22,3%), scintigraphy with 99mТс-MIBI (31,4%), genetic consultation and DNA-diagnostics via sequencing by Senger (21,8% and 16,8%). Morphological study of myocardium was done in 84 (38,2%) patients, incl. 52 endomyocardial biopsies (EMB) with PCR for parvovirus B19 genome and herpes viruses. Results. By the data of clinical-morphological assessment, viral genome in blood was revealed in 21% patients, in myocardium — 52%, definite myocarditis was set in 48%, possible — 8%, genetical DCMP — in 12%, myocarditis with genetic cardiomyopathy — 23% (incl. those with pathogenic mutations in genes MYBPC3, DSP, DSG2, LMNA, EMD, DES, TTR, DTNA), idiopathic DCMP — in 9%. In 59% patients myocarditis was primarily chronic, in more than one third of patients there was combination of several causes for DCMP (incl. alcohol). Short-term and long-term results of treatment were evaluated in 127 patients with myocarditis: 52 virus-positive by blood and/or myocardium (myocarditis morphologically proved in 73,1%) and 75 virus-negative (biopsy in 30,7%), that differed by a little lower EDS LV and lower EF. Significant differences by immunity activation (titres of anticardial antibodies) were not found; in 7% there was isolated viral myocarditis, in 34% — viral-immune; in 59% — immune. If viruses were found, therapy ordered with acyclovir, gancyclovir, entecavir, i. v. immunoglobulines; elimination of virus from the blood reached in 81% of patients. If there was tolerance to cardiotropic therapy and high immune activity, immune suppression therapy (IST) was ordered: in 51% of virus-positive and 62,7% virus-negative patients: steroids 30 [22; 40] and 24 [16; 32] mg/day, azathioprin 1-2 mg/kg, hydroxychloroquine 200 mg/day. In 12,0 [6,0; 20,0] months it was found that only in IST group there was remarkable decrease of CHF FC, LV sizes, MPPA and increase of EF LV from 30,3±10,6% to 39,2±11,9% independently from presence or absence of viral genome. In absence of IST such dynamics was not found. The best results were found in virus-negative patients receiving IST (mortality 9,8%, need for surgical treatment 21,3%), the worst — in virus-positive patients without IST (66,7% and 61,1%, respectively). Conclusion . Nosological nature of DCMP syndrome can be defined in most cases; usually there is myocaditis in its origin. IST in high immune activity of myocarditis (high titers of anticardial antibodies) leads to significant increase of EF, decrease of the left ventricle size, MPPA, mortality and necessity of surgery in virus-negative, as in virus-positive patients.

Electrical Rhythms Revealed by Harmonic Analysis of a High-Resolution Cardiogram.

The front-end low-noise electronic amplifiers and high-throughput computing systems made it possible to record ECG with a high resolution in the low-frequency range including the respiration and Mayer frequencies and to analyze ECG with digital filtering technique and harmonic analysis. These tools yielded ECG spectra of narcotized rats, which contained the characteristic pulsatile triplets and pentaplets with splitting constant equal to respiration rate, as well as the peaks at respiration and Mayer frequencies. The harmonic analysis of ECG determined the frequency parameters employed to tune the software bandpass filters, which revealed the respiratory (R) and Mayer (M) waves in the time domain with the amplitudes of 20-30 μV amounting to 5% ECG amplitude. The depolarizing myorelaxant succinylcholine chloride capable to trigger various types of arrhythmias, transiently increased R-wave, inhibited M-wave, and provoked a negative U-wave within a heartbeat ECG cycle synchronously with inspiration. It is hypothesized that M-, R-, and U-waves in ECG reflect cardiotropic activity of autonomic nervous system. The respective spectral peaks in ECG can be employed to assess intensity of sympathetic and parasympathetic cardiotropic influences, their balance, and the risk of arrhythmias.

The homologous rat chromogranin A1‐64 (rCGA1‐64) modulates myocardial and coronary function in rat heart to counteract adrenergic stimulation indirectly via endothelium‐derived nitric oxide

Chromogranin A (CGA), produced by human and rat myocardium, generates several biologically active peptides processed at specific proteolytic cleavage sites. A highly conserved cleavage N-terminal site is the bond 64-65 that reproduces the native rat CGA sequence (rCGA1-64), corresponding to human N-terminal CGA-derived vasostatin-1. rCGA1-64 cardiotropic activity has been explored in rat cardiac preparations. In Langendorff perfused rat heart, rCGA1-64 (from 33 nM) induced negative inotropism and lusitropism as well as coronary dilation, counteracting isoproterenol (Iso) - and endothelin-1 (ET-1) -induced positive inotropic effects and ET-1-dependent coronary constriction. rCGA1-64 also depressed basal and Iso-induced contractility on rat papillary muscles, without affecting calcium transients on isolated ventricular cells. Structure-function analysis using three modified peptides on both rat heart and papillary muscles revealed the disulfide bridge requirement for the cardiotropic action. A decline in Iso intrinsic activity in the presence of the peptides indicates a noncompetitive antagonistic action. Experiments on rat isolated cardiomyocytes and bovine aortic endothelial cells indicate that the negative inotropism observed in rat papillary muscle is probably due to an endothelial phosphatidylinositol 3-kinase-dependent nitric oxide release, rather than to a direct action on cardiomyocytes. Taken together, our data strongly suggest that in the rat heart the homologous rCGA1-64 fragment exerts an autocrine/paracrine modulation of myocardial and coronary performance acting as stabilizer against intense excitatory stimuli.

Cardiovascular properties of aqueous extract from <i>Tapinanthus dodoneifolius</i> DC Danser

Aqueous extracts of Tapinanthus dodoneifolius DC Danser. (Loranthaceae) (AETD) were investigated for cardiovascular activities on isolated rat aorta and heart. AETD did not affect heart rate but significantly enhanced heart contraction force and relaxation capacity. AETD (0.001-1mg/ml) elicited a dose-dependent relaxation on arteries which was previously contracted with phenylephrine [10-6M] (rat aorta). AETD induces relaxation in endothelium dependent manner. When Indomethacin failed to inhibit AETD vasodilatory activity, in the presence of L-NAME, the vasodilatory activity of AETD was completely abolished. These results suggest a cardiotropic activity without any tachycardia as a side effect for AETD. However, AETD elicited vasodilatory activity which involved NO from endothelium. Key words : Tapinanthus dodoneifolius, endothelium , vasodilator , rat. Afr. J. Trad. Comp. Alt. Med. , 2005, 2 (1): 25-30

Biological evaluation of analogues of an insect neuropeptide proctolin.

Continuing our studies on proctolin (Arg-Tyr-Leu-Pro-Thr) we performed the synthesis and biological evaluation of 52 analogues substituted in position 2, 3, 4, and 5 of the peptide chain. The peptides were bioassayed for cardiotropic activity in vitro on Tenebrio molitor and myotropic activity on foregut of Schistocerca gregaria. Twenty analogues retained 20-80% of proctolin activity.

Biological evaluation of analogues of an insect neuropeptide proctolin.

Continuing our studies on proctolin (Arg-Tyr-Leu-Pro-Thr) we performed the synthesis and biological evaluation of 52 analogues substituted in position 2, 3, 4, and 5 of the peptide chain. The peptides were bioassayed for cardiotropic activity in vitro on Tenebrio molitor and myotropic activity on foregut of Schistocerca gregaria. Twenty analogues retained 20-80% of proctolin activity.

GH‐independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy

To investigate acute cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to ischemic (iCMP) and dilated cardiomyopathy (dCMP). We studied the effect of intravenous hexarelin administration on growth hormone (GH) levels and left ventricular ejection fraction (LVEF) evaluated by radionuclide angiography in eight patients with dCMP (age 53.0+/-2.8, LVEF 16.7+/-2.1%) and five patients with iCMP (age 52.0+/-2.8 years, LVEF 22.6+/-2.1). Results were compared with a group of seven normal subjects (age 37.4+/-3.4 years, LVEF 64.0+/-1.5%) and seven patients with severe growth-hormone deficiency (GHD; age 42.0+/-4.4 years, LVEF 50.0+/-1.9%) previously studied with the same methodology. In dCMP and iCMP patients hexarelin induced a similar significant (P<0.05) increase in GH levels. In iCMP patients hexarelin induced a LVEF increase (peak LVEF 26.2+/-2.5%, P<0.05) as observed in normals and GHD, while in dCMP LVEF was unchanged (peak LVEF 17.7+/-1.7, P=NS). In all groups other hemodynamic parameters were unchanged. Acute hexarelin administration increases LVEF in iCMP patients (as in normals and GHD) but not in dCMP patients in spite of a similar GH releasing effect and basal LVEF. A possible explanation of the positive inotropic effect of hexarelin in iCMP could be a direct stimulation on viable myocardium or myocardial contractile reserve.