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There is a growing appreciation that regulation of muscle contraction requires both thin filament and thick filament activation in order to fully activate the sarcomere. The prevailing mechano‐sensing model for thick filament activation was derived from experiments on fast‐twitch muscle. We address the question whether, or to what extent, this mechanism can be extrapolated to the slow muscle in the hearts of large mammals, including humans. We investigated the similarities and differences in structural signatures of thick filament activation in porcine myocardium as compared to fast rat extensor digitorum longus (EDL) skeletal muscle under relaxed conditions and sub‐maximal contraction using small angle X‐ray diffraction. Thick and thin filaments were found to adopt different structural configurations under relaxing conditions, and myosin heads showed different changes in configuration upon sub‐maximal activation, when comparing the two muscle types. Titin was found to have an X‐ray diffraction signature distinct from those of the overall thick filament backbone, and its spacing change appeared to be positively correlated to the force exerted on the thick filament. Structural changes in fast EDL muscle were found to be consistent with the mechano‐sensing model. In porcine myocardium, however, the structural basis of mechano‐sensing is blunted suggesting the need for additional activation mechanism(s) in slow cardiac muscle. These differences in thick filament regulation can be related to their different physiological roles where fast muscle is optimized for rapid, burst‐like, contractions, and the slow cardiac muscle in large mammalian hearts adopts a more finely tuned, graded response to allow for their substantial functional reserve. Key points: Both thin filament and thick filament activation are required to fully activate the sarcomere.Thick and thin filaments adopt different structural configurations under relaxing conditions, and myosin heads show different changes in configuration upon sub‐maximal activation in fast extensor digitorum longus muscle and slow porcine cardiac muscle.Titin has an X‐ray diffraction signature distinct from those of the overall thick filament backbone and this titin reflection spacing change appeared to be directly proportional to the force exerted on the thick filament.Mechano‐sensing is blunted in porcine myocardium suggesting the need for additional activation mechanism(s) in slow cardiac muscle.Fast skeletal muscle is optimized for rapid, burst‐like contractions, and the slow cardiac muscle in large mammalian hearts adopts a more finely tuned graded response to allow for their substantial functional reserve. [ABSTRACT FROM AUTHOR]

This article discusses the first cardiac xenotransplant performed on a consciously consenting human. Xenotransplantation, the transplantation of organs from animals to humans, is seen as a potential solution to the shortage of human organs available for transplantation. However, there are various risks and considerations associated with xenotransplantation, including zoonotic disease transmission, lifelong monitoring, animal welfare issues, and psychosocial impacts on recipients. The article highlights the need for comprehensive psychiatric evaluation and support for patients undergoing xenotransplantation, both before and after the procedure. It also emphasizes the importance of preparing patients for potential media exposure and the disclosure of private health information. The case discussed in the article reveals the challenges and shortcomings in the current approach to psychiatric assessment and support in xenotransplantation cases. The authors suggest the development of standardized guidelines and a multidisciplinary approach to address the unique challenges of xenotransplantation. [Extracted from the article]

Background: The study was performed to compare the efficacy and safety during radiofrequency ablation (RFA) using ThermoCool SmartTouch (ST) and ThermoCool SmartTouch‐SF (STSF) catheters in the porcine heart. Methods and Results: RFA was performed on the porcine myocardium by using two irrigated ablation catheters. Three groups were divided based on the different contact forces (CFs): low contact force (LCF) (1–3 g), medium contact force (MCF) (5–10 g), and high contact force (HCF) (15–20 g). In each group, RFA was delivered at four power settings of 30, 40, 50, 60 W. At each power, RFA was applied to reach the target ablation index (AI) of 350, 450, and 500. Altogether, 360 RF lesions were created by using 72 ablation conditions. AI value was positively correlated with lesion size using ST and STSF catheters. At a fixed power, lesion dimensions significantly smaller in the LCF group, whereas did not differ between MCF and HCF groups. Furthermore, at a fixed CF, lesion dimensions increased with power set at 40 W compared with 30 W but decreased with high‐power RF energy (50 and 60 W). Although the average lesion surface diameter and the maximum diameter was increased using the STSF catheter, there were no significant differences in LV between the two catheters. The steam pop provoked more frequently using ST catheter and showed a negative correlation with CF and positive correlation with high‐power energy. Conclusion: The STSF catheter is safer and equally effective in lesion formation compared with the ST catheter. LV was increased along with the early increase of CF and power, whereas a further increase of CF and power significantly reduces the lesion size. [ABSTRACT FROM AUTHOR]

Abstract Background Endothelial cells (ECs) play a key role in tissue homeostasis, in several pathological conditions, and specifically in the control of vascular functions. ECs are frequently used as in vitro model systems for cardiovascular studies and vascular biology. The porcine model is commonly used in human clinical cardiovascular studies. Currently, however, there is no robust protocol for the isolation of porcine heart ECs. We have developed a fast isolation protocol, which is cost effective, takes only 1–2 h, and produces EC purity of over 97%. This protocol is optimized for porcine hearts but can be adapted for use with other large animals. Methods Heart is washed by flushing with PBS, whereafter endothelial cells are detached by collagenase incubation and the cells can then be collected immediately after the incubation and plated within an hour after the heart is isolated from a pig. Results The swiftness of the protocol limits changes in the phenotype and RNA expression profile of the cells. Cells were identified as ECs with CD31 (PECAM-1) antibody immunostaining. Functionality of ECs were ensured with in vitro angiogenesis assay. The purity of the ECs was verified by using fluorescence assisted cell sorting (FACS) with the CD31 antibody. Conclusion We developed a new, fast, and cost-effective isolation method for pig heart ECs. Successful isolation of pure ECs is a prerequisite for several cardiovascular and vascular biology studies.

Diagnosis of ischaemia-related sudden cardiac death in the absence of microscopic and macroscopic ischaemic lesions remains a challenge for medical examiners. Medical imaging techniques increasingly provide support in post-mortem examinations by detecting and documenting internal findings prior to autopsy. Previous studies have characterised MR relaxation times to investigate post-mortem signs of myocardial infarction in forensic cohorts. In this prospective study based on an ex situ porcine heart model, we report fundamental findings related to intramyocardial variability and temporal stability of T2 as well as the effects of permanent coronary occlusion on T2 and T2∗ relaxation in post-mortem myocardium. The ex situ porcine hearts included in this study (n= 19) were examined in two groups (Ss, n= 11 and Si, n= 8). All magnetic resonance imaging (MRI) examinations were performed ex situ, at room temperature and at 3 T. In the Ss group, T2 mapping was performed on slaughterhouse porcine hearts at different post-mortem intervals (PMI) between 7 and 26 h. Regarding the intramyocardial variability, no statistically significant differences in T2 were observed between myocardial segments (p= 0.167). Assessment of temporal stability indicated a weak negative correlation (r=− 0.21) between myocardial T2 and PMI. In the Si group, animals underwent ethanol-induced complete occlusion of the left anterior descending artery. T2 and T2∗ mapping were performed within 3 h of death. Differences between the expected ischaemic and remote regions were statistically significant for T2 (p= 0.007), however not for T2∗ (p= 0.062). Our results provide important information for future assessment of the diagnostic potential of quantitative MRI in the post-mortem detection of early acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Myocardium passive mechanical response has been a major topic of study for decades due to its major impact on cardiac physiology. Here, we propose a novel modeling methodology that integrates both in vivo and in vitro data to estimate the tissue mechanical parameters for a particular orthotropic hyperelastic model as those proposed by Costa and by Holzapfel & Ogden, although it can be easily extended to any other. In vitro biaxial and triaxial shear extension tests were conducted in biopsied samples and in vivo pressure-volume recordings were obtained. Left ventricle (LV) geometry was reconstructed using magnetic resonance imaging (MRI) and pressure gradients during ventricular inflation were recorded with the Catheter Conductance Method (CCM). Finally, a Finite Element (FE) in vivo LV model was implemented to get the material model parameters using an inverse approach that uses a minimization process combining both the in vivo and in vitro available data. Our results demonstrate that the parameters obtained solely from in vitro testing (IVT), or from in vivo passive inflation (IVV) do not provide satisfactory fits for both responses simultaneously ( R 2 I V T t e s t s = 0.977 , R 2 I V T P V = 0.697 and R 2 I V V t e s t s = 0.687 , R 2 I V V P V = 0.995). On the contrary, the proposed combined in vitro & in vivo optimization process (MIN) converges to a solution that effectively captures both the in vivo and in vitro behaviors ( R 2 M I N t e s t s = 0.815 , R 2 M I N P V = 0.992). Thus, this novel combined approach offers a comprehensive framework for accurately characterizing myocardial mechanical behavior. The obtained parameters can serve as a basis for further cardiac simulations and contribute to a better understanding of cardiac mechanics and function. • Modeling the passive behavior of myocardium is essential in understanding heart function and in tissue engineering. • Material parameters obtained from in vitro experimental tests provide bad results in in vivo applications. • Parameters derived from in vivo images prevent capturing local anisotropy and getting a good representation of stresses. • Combining biaxial and shear tests with in vivo images allows to reproduce heart function and in vitro results. • The proposed method permits accurate cardiac simulations and a better understanding of cardiac mechanics. [ABSTRACT FROM AUTHOR]

Background: Endothelial cells (ECs) play a key role in tissue homeostasis, in several pathological conditions, and specifically in the control of vascular functions. ECs are frequently used as in vitro model systems for cardiovascular studies and vascular biology. The porcine model is commonly used in human clinical cardiovascular studies. Currently, however, there is no robust protocol for the isolation of porcine heart ECs. We have developed a fast isolation protocol, which is cost effective, takes only 1-2 h, and produces EC purity of over 97%. This protocol is optimized for porcine hearts but can be adapted for use with other large animals. Methods: Heart is washed by flushing with PBS, whereafter endothelial cells are detached by collagenase incubation and the cells can then be collected immediately after the incubation and plated within an hour after the heart is isolated from a pig. Results: The swiftness of the protocol limits changes in the phenotype and RNA expression profile of the cells. Cells were identified as ECs with CD31 (PECAM-1) antibody immunostaining. Functionality of ECs were ensured with in vitro angiogenesis assay. The purity of the ECs was verified by using fluorescence assisted cell sorting (FACS) with the CD31 antibody. Conclusion: We developed a new, fast, and cost-effective isolation method for pig heart ECs. Successful isolation of pure ECs is a prerequisite for several cardiovascular and vascular biology studies. [ABSTRACT FROM AUTHOR]

Meat byproducts, such as the internal organs from slaughtered animals, are usually underutilized materials with low commercial value. The functional (emulsifying, gelling, and foaming) properties of soluble protein extracts derived from pork hearts were investigated, as well as their molecular weight distribution. A central composite design (CCD) for two process variables (pH and ionic strength of the extraction buffer) was used to foreknow the effects of the process conditions on the physicochemical characteristics and technofunctionality of the protein extracts by means of the response surface methodology (RSM). SDS-PAGE patterns of the heart protein solutions revealed multiple bands with molecular weights ranging from 15 to 220 kDa, mainly corresponding to sarcoplasmic, myofibrillar, as well as blood proteins. The best extraction conditions to obtain protein fractions with good foaming properties would correspond to acid pH (pH ≤ 5) and high salt content (2–4%). On the contrary, solutions recovered at pH > 5 with low NaCl contents were the ones showing better emulsifying properties. Regarding gelation ability, heat-induced gels were obtained from extracts at pH 6.5–8, which showed improved firmness with increasing NaCl content (2–4%). Satisfactory second-order polynomial models were obtained for all the studied response variables, which can be useful in guiding the development of functional ingredients tailored for specific uses to maximize applications.

Purpose: Contact force (CF) catheters are useful to address proper contact during ablation. However, interactions between the ablation process, or its associated irrigation flow changes, with the CF sensing may translate into unexpected CF value fluctuations. We aimed to test for unintentional CF value variations during radiofrequency applications at a fixed applied force, with two commercially available catheters (TactiCath™ and SmartTouch™), and to evaluate its theoretical clinical significance by correlating CF-derived automatic ablation algorithms (force-time integral and lesion index) and actual lesion size at two standard CF values.Methods: Four series of 20 perpendicular epicardial ablations (20 W, 60 s, 17 ml/min) were performed on porcine left ventricle submerged in 37 °C saline. Catheters were mechanically fixed at a constant position and evaluated at 10 and 20 g. CF values were digitally analysed before each application changing irrigation rate (2-17-30 ml/min), and during ablation. Finally, lesions were quantified.Results: Increasing irrigation before ablation led to a slight but significant CF decrease. During ablation, CF showed a reproducible pattern: fast initial decrease, subsequent increase until higher-than-initial values and final plateau phase (CF variation up to 69% at 10 g). CF variability was significantly higher at 10 g and using TactiCath™. There were no major differences in lesion size between catheters at the same initial CF. CF only correlated mildly to lesion measures, and automatic algorithms globally failed to predict lesion size.Conclusions: CF measured values spontaneously vary during ablation following a predictable pattern (initial decrease, subsequent increase and final plateau). This is especially remarkable applying lower CF. [ABSTRACT FROM AUTHOR]

Much attention has been focused on the passive mechanical properties of the myocardium, which determines left ventricular (LV) diastolic mechanics, but the significance of the visceral pericardium (VP) has not been extensively studied. A unique en face three-dimensional volumetric view of the porcine VP was obtained using two-photon excitation fluorescence to detect elastin and backscattered second harmonic generation to detect collagen, in addition to standard light microscopy with histological staining. Below a layer of mesothelial cells, collagen and elastin fibers, extending several millimeters, form several distinct layers. The configuration of the collagen and elastin layers as well as the location of the VP at the epicardium providing a geometric advantage led to the hypothesis that VP mechanical properties play a role in the residual stress and passive stiffness of the heart. The removal of the VP by blunt dissection from porcine LV slices changed the opening angle from 53.3 ± 10.3 to 27.3 ± 5.7° (means ± SD, P < 0.05, a 4). In four porcine hearts where the VP was surgically disrupted, a significant decrease in opening angle was found (35.5 ± 4.0°) as well as a rightward shift in the ex vivo pressure-volume relationship before and after disruption and a decrease in LV passive stiffness at lower LV volumes (P < 0.05). These data demonstrate the significant and previously unreported role that the VP plays in the residual stress and passive stiffness of the heart. Alterations in this layer may occur in various disease states that effect diastolic function. [ABSTRACT FROM AUTHOR]

The morphology of the vascular supply of peripheral branches of cardiac nerves has not been systematically described until now. The aim of this study was to describe the architectonics of the vasa nervorum of epicardial nerves in porcine hearts by using two injection techniques. Twenty-three hearts from young healthy pigs were used. In 10 hearts India ink solution was injected into the origin of the anterior interventricular branch. In another 10 hearts India ink solution was injected retrogradely through the coronary sinus. The hearts were then analyzed using a magnifying glass and light microscopy. The arterial injection showed the entirety of the rich venous components of the vasa nervorum, which often consisted of paired veins accompanying the epicardial nerves. The thickness of the nerves ranged from 50 to 815 μm. The vasa nervorum drained into larger subepicardial veins. In seven of the hearts prepared with venous injections the vasa nervorum of epicardial nerves were visualized in the same detail as in the arterial preparations and India ink solution filled the right ventricle via the smallest cardiac veins. The histological analysis of these seven hearts showed complete dehiscence and functional insufficiency of small and larger veins valves. In the other three hearts prepared with venous injections the valves were competent, which prevented retrograde filling of larger and smaller veins. The results obtained expand the current knowledge on epicardial nerves vasa nervorum and provide anatomical evidence behind the mechanism of retrograde application of cardioplegic solutions in cardiac surgery., (© 2021 American Association for Anatomy.)

Background: Radiofrequency catheter ablation of atrial flutter, atrial fibrillation or ventricular tachycardia may be favoured by large lesions. We compared lesions created in unipolar mode using 10-mm/8 F electrodes with those of 4-mm/7 F catheters. Methods: Ablations were first performed in porcine hearts in vitro (70°C, 60 s, tangential catheter tip-tissue orientation). Anaesthetized pigs were thereafter ablated with 10- or 4-mm catheters in the right atrial free wall (RAFW), inferior vena cava-tricuspid valve (IVC-TV) isthmus and left ventricle (LV). Results: In vitro, lesion length doubled and lesion volume tripled using the 10-mm catheter. Average power supply was 69 (SD12) (10-mm tip) versus 26 (SD7) W (4-mm tip). In vivo, lesion length increased by 50% and lesion volume fivefold. Charring at the lesion surface or sudden impedance rises were not observed in vivo. Histologically, coagulation necrosis and minor haemorrhages were found. One RAFW lesion (10-mm) showed a dissection approaching the epicardium. Fibrinous platelet clots or overt thromboses covered the endocardial surface in half of all lesions. Three 10-mm electrode isthmus lesions extended to the right descending posterior artery and one LV lesion to the left anterior descending artery, but there was no damage to the arterial walls. Following six ablations with the 10-mm electrode and two with the 4-mm tip, injury to the adjacent lung tissue of 0.5 to 6.0 mm depth was found (p = 0.22). Conclusion: RF ablation using 10-mm/8 F electrodes created significantly larger lesions. 10-mm electrodes appeared safe in the porcine IVC-TV isthmus and LV, but not in the RAFW. [ABSTRACT FROM AUTHOR]

Aims Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. Methods and Results In vitro, confluent lesions were reliably created by a ‘dielectrode’ catheter (energy delivered simultaneously (in parallel) from two 4mm electrodes spaced 1mm apart, towards an indifferent electrode), and a ‘bipolar’ catheter (energy delivered (in series) between two 4mm electrodes spaced 5mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30s duration (70°C) were administered to the inferior vena cava–tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length×width×depth measured 7·4 (2·4)×5·4 (2·2)×2·8 (0·8)mm in the standard unipolar mode, 10·2 (1·4)×6·3 (0·7)×3·3 (1·1)mm in the dielectrode mode and 14·0 (3·6)×6·0 (1·7)×3·8 (1·2)mm in the bipolar mode. Thus lesion length increased significantly through the three groups (P<0·001), while width and depth did not. Conclusion Both dielectrode and bipolar ablation were feasible in porcine right atrial ablation, and created longer lesions than the standard unipolar mode. By allowing a larger interelectrode distance, bipolar ablation created the longest lesions and may be favourable when linear lesions are necessary. [ABSTRACT FROM PUBLISHER]

We have isolated an endogenous positive inotropic factor (EPIF) from porcine left heart ventricular tissue, which demonstrated to have only weak digitalis-like properties including the inhibition of myocardial Na+,K+-ATPase. EPIF completely lacks digitalis-like toxicity such as after-contractions in larger doses. In our recent studies, we have demonstrated that EPIF produces a decrease in the amplitude of the post-rest rapid cooling contracture which indicated that EPIF may release Ca2+from the sarcoplasmic reticulum. In the present study, the effects of EPIF were investigated on the Ca2+uptake and release properties of SR enriched membrane vesicles from rat heart. At pH 6.8 and in the presence of oxalate, EPIF dose-dependently inhibited the ATPdependent uptake of Ca2+by SR vesicles. Concentrations as low as 25 ul (in 1 mL uptake medium) of EPIF caused a 45-47% reduction in the uptake of Ca2+within 3-4 min. Increases in EPIF concentration to 50 ul/mL caused additional reduction of only 15-20% in the uptake of Ca2+. Concentrations of 25 ul/mL of EPIF had little or no effects on passive release of actively loaded Ca2+in SR vesicles. On doubling the concentrations to 50 ul/mL EPIF, however, enhanced the release of Ca2+by 25-28% during 1-2 min. and 44-48% after 4 min of incubation of Ca2+loaded vesicles in the release medium. Relatively smaller effects of EPIF on Ca2+release implies that EPIF may mainly lower the uptake of Ca2+in SR. This reduced uptake of Ca2+may be explained by the EPIF-induced inhibition of Ca2+pump. [ABSTRACT FROM AUTHOR]

Stereoisomers often exhibit differences in their pharmacological activities. Therefore, the phosphodiesterase inhibitory effects of the cardiotonic agent saterinone in form of the racemate were investigated in comparison with the inhibitory properties of its enantiomers R(+)- and S(−)-saterinone. For this purpose the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts and porcine hearts were separated by DEAE-sepharose anion exchange chromatography. Four different phosphodiesterase isoenzymes were isolated from failing human myocardium and designated phosphodiesterase I-IV. Three phosphodiesterase isoenzymes could be separated from ventricular tissue of porcine hearts. A Ca/calmodulin stimulated phosphodiesterase I was not detectable in porcine myocardium. In failing human hearts racemic saterinone was a potent inhibitor of phosphodiesterase III (IC 0.02 μmol/l) and IV (IC 0.03 μmol/l) as compared to the inhibition of phosphodiesterase I (IC 37.3 μmol/l) and II (IC 51.4 μmol/l). In comparison with the racemate, R(+)- and S(−)-saterinone showed only slight differences in their phosphodiesterase inhibitory effects. R(+)-saterinone inhibited phosphodiesterase III slightly but significantly more potently and selectively than did S(−)-saterinone. Compared to the inhibition of phosphodiesterase I and II both enantiomers were similarly potent and selective inhibitors of phosphodiesterase III and IV. Similar results were obtained in porcine hearts. It is concluded that the racemate saterinone and its enantiomers R(+)- and S(−)-saterinone are virtually equipotent concerning the inhibition of phosphodiesterase isoenzymes isolated from failing human hearts or porcine ventricular tissue. The enantiomers of saterinone did not exhibit distinct stereoselectivity in their phosphodiesterase inhibitory effects. [ABSTRACT FROM AUTHOR]

Objective: Angiogenesis in the porcine heart can be induced by myocardial ischaemia following vascular occlusions. This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis. Methods: Experimental ischaemia and subsequent focal necroses were induced by selective injection of 25 μm microspheres into the left circumflex artery. The hearts were excised after 3–168 h of microembolisation, and tissue was collected from a non-ischaemic control area and the circumflex region of the same heart for further analysis. Results: IGF-I was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, IGF-I mRNA expression was significantly increased in the experimental region (1.8-fold) after 72 h and to a lesser extent after 168 h. In the ischaemic region, characterised by capillary sprouting, numerous mononuclear cells contained IGF-I mRNA. In contrast, IGF-II mRNA levels, constitutively produced by porcine myocytes, were not altered by microembolisation. IL-1α, IL-1β, and IL-4 mRNA expression was undetectable in our animal model, whereas IL-6 was constitutively transcribed in normal and ischaemic heart and remained insensitive to microembolisation and focal necrosis. Conclusion: After microembolisation, increased IGF-I mRNA expression occurred by infiltrating monocytes in areas of microsphere induced focal necrosis, where capillary sprouting can be detected, suggesting that IGF-I is involved in inflammation linked angiogenic processes. [ABSTRACT FROM PUBLISHER]

Objective: Previous observations have shown that myocardium activates many adaptive processes after brief ischaemia. The aim of this study was to determine whether insulin-like growth factors (IGF) as well as their receptors and binding proteins (IGFBP), which control the activity of the IGF, may play an important role during these processes. Methods: Ischaemia was induced in anaesthetised open chest pigs by two 10 min occlusions of the left anterior descending coronary artery, separated by 30 min of reperfusion, and followed by reperfusion up to 210 min. Tissue from the ischaemic area and from a non-ischaemic control region of the same heart was examined by means of northern blot, slot blot, and in situ hybridisation. Results: IGF-I, IGF-II, the type I receptor, the insulin receptor, and IGFBP-2-6 are constitutively expressed in porcine myocardium. In situ hybridisation showed that IGF-I and IGF-II are mainly transcribed by myocytes. Ischaemia/reperfusion led to an early and significant increase in IGF-II mRNA compared to non-sham controls but not in comparison with sham operated animals, which already showed a (not significantly) enhanced IGF-II expression. In each case the IGF-II mRNA levels are equal in the control and the experimental region of the same heart. Whereas IGF-II expression was already increased by experimental stress, IGFBP-5 mRNA was enhanced only by ischaemia/ reperfusion. The expression of IGF-I, the receptors, and IGFBP-2, 3, 4, and 6 remained unchanged during the experimental protocol. IGFBP-1 was neither expressed nor induced in our model. Conclusions: IGF-II acts like a stress-response gene activated by the experimental conditions (surgery, anaesthesia) and remains induced during following episodes of ischaemia/reperfusion. A possible interaction of IGFBP-5 with other components of the IGF system may contribute to the preconditioning response. [ABSTRACT FROM PUBLISHER]

Objective: Brief coronary occlusions cause upregulation of expression in a wide variety of genes. These changes in tissue mRNA concentration could have been produced by transcriptional or post-transcriptional events. The aim of this study was to discriminate between increased transcription and changes in mRNA stability using run-on assays with isolated myocyte nuclei. Methods: Myocyte nuclei isolated from ischaemic/ reperfused and normal myocardium were incubated with labelled ribonucleotides. The radioactive RNA was then hybridised with specific cDNA probes and slot blots were autoradiographed. Results: There was increased transcriptional activity for the proto-oncogenes c-myc, c-jun, jun-B, and jun-D. There were marked increases in transcriptional activity for sarcoplasmic Ca2+-ATPase. calmodulin, phospholamban, and calsequestrin. Strong transcriptional activity was found for the ubiquitin and heat shock protein (hsp27, hsp70) genes, and for PAI-1 and GAPDH. The transcription for the β myosin heavy chain gene was not altered. Conclusions: Changes in the tissue concentration of mRNA species following brief coronary occlusion and reperfusion are most often the result of altered transcriptional activity. Increased c-fos mRNA concentrations observed in earlier studies cannot be explained by transcriptional activity of myocytes during reperfusion. Calmodulin is strongly transcribed but tissue concentration stays constant. The overall pattern of gene expression is indicative of damage at the molecular level, and calcium binding proteins (among perhaps many others) are in need of repair.Cardiovascular Research 1994;28:1062-1069 [ABSTRACT FROM PUBLISHER]

Objective: The aim was to examine the expression of ubiquitin (Ub), 27 kDa heat shock protein (hsp27), and hsp60 mRNA in normal and briefly ischaemic and reperfused porcine myocardium: Methods: The left anterior descending coronary artery was occluded for two periods of 10 min separated by 30 min of reperfusion. After the second occlusion the myocardium was reperfused up to 210 min. Tissue from ischaemic, ischaemic-reperfused, and non-ischaemic regions of the heart was analysed by northern and slot blot hybridisation and nuclear run-on transcription assays employing radiolabelled cDNA probes for Ub, hsp27, and hsp60, as well as by western blot using monoclonal antibodies recognising Ub protein conjugates and antiserum recognising hsp27. Results: Systolic wall thickening was significantly decreased at 30 min reperfusion after both occlusions and remained depressed at longer periods of reperfusion. Using northern blot hybridisations, several mRNAs encoding Ub, 0.9 kb mRNA encoding hsp27, and 2.2 kb mRNA encoding hsp60 were detected in sham operated, non-ischaemic, and ischaemic myocardial tissues. Densitometric analysis of northern and slot blot hybridisation signals showed significant increase of basal tissue levels of Ub mRNA in stunned regions only during the 30 min of the second reperfusion period. Increased levels of hsp27 mRNA in stunned tissue were already noted at the first ischaemic period and were sustained compared to control during the subsequent periods of reperfusion. Changes in hsp60 mRNA tissue levels were not observed during ischaemia and subsequent reperfusions. Transcription of the Ub and hsp27 genes was increased during 30 and 120 min of the second reperfusion period. The transient enhancement of tissue levels of Ub mRNA was associated with temporary formation of new Ub-protein conjugates. However, the increased synthesis of mRNA encoding hsp27 was not followed by changes of hsp27 protein content in myocardial tissue. Conclusions: The findings support the hypothesis that molecular damage occurs in stunned myocardium; however, the target molecules remain to be recognised.Cardiovascular Research 1993;27:1421-1429 [ABSTRACT FROM PUBLISHER]

Meat byproducts, such as the internal organs from slaughtered animals, are usually underutilized materials with low commercial value. The functional (emulsifying, gelling, and foaming) properties of soluble protein extracts derived from pork hearts were investigated, as well as their molecular weight distribution. A central composite design (CCD) for two process variables (pH and ionic strength of the extraction buffer) was used to foreknow the effects of the process conditions on the physicochemical characteristics and technofunctionality of the protein extracts by means of the response surface methodology (RSM). SDS-PAGE patterns of the heart protein solutions revealed multiple bands with molecular weights ranging from 15 to 220 kDa, mainly corresponding to sarcoplasmic, myofibrillar, as well as blood proteins. The best extraction conditions to obtain protein fractions with good foaming properties would correspond to acid pH (pH ≤ 5) and high salt content (2–4%). On the contrary, solutions recovered at pH > 5 with low NaCl contents were the ones showing better emulsifying properties. Regarding gelation ability, heat-induced gels were obtained from extracts at pH 6.5–8, which showed improved firmness with increasing NaCl content (2–4%). Satisfactory second-order polynomial models were obtained for all the studied response variables, which can be useful in guiding the development of functional ingredients tailored for specific uses to maximize applications. [ABSTRACT FROM AUTHOR]

The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves., (© 2020 Wiley Periodicals LLC.)

The aim of the study was to investigate the existence of valves in small peripheral coronary veins of porcine hearts. The study was performed on 20 porcine hearts using standard histological methods. The veins in the subepicardial and intramyocardial regions of the anterior and posterior parts of the interventricular septum and in the wall of the right atrium were studied. Valves were present in intramyocardial veins (diameter of 75-180 μm), in the veins located just beneath the external surface of the myocardium (diameter 120-170 μm) and in the terminal segments of the ventricular veins (diameter 250 μm) opening into the stems of the anterior interventricular vein and middle cardiac vein. Valves were also recorded in most veins of the subepicardial space. The described rich presence of valves in the small coronary veins may contribute to a better comprehension of their hemodynamic properties. These findings may also help to improve the understanding of the efficacy of retrograde application of medications, a novel technique in cardiology and cardiac surgery., (© 2019 Wiley Periodicals, Inc.)

Intracardiac blood flow patterns are affected by the morphology of cardiac structures and are set up to support the heart's pump function. Exercise affects contractility and chamber size as well as pre‐ and afterload. The aim of this study was to test the feasibility of four‐dimensional phase contrast cardiovascular MRI under pharmacological stress and to study left ventricular blood flow under stress. 4D flow data were successfully acquired and analysed in 12 animals. During dobutamine infusion, heart rate and ejection fraction increased (82 ± 5 bpm versus 124 ± 3 bpm/46 ± 9% versus 65 ± 7%; both p < 0.05). A decrease in left ventricular end‐diastolic volume (72 ± 14 mL versus 55 ± 8 mL; p < 0.05) and end‐systolic volume (40 ± 15 mL versus 19 ± 6 mL; p < 0.05) but no change in stroke volume were observed. Trans‐mitral diastolic inflow velocity increased under dobutamine and the trajectory of inflowing blood was directed towards the anterior septum with increased inflow angle (26 ± 5°) when compared with controls (15 ± 2°). In 5/6 animals undergoing stress diastolic vortices developed later, and in 3/6 animals vortices collapsed earlier with significantly smaller cross‐sectional area during diastole. The vorticity index was not affected. Under the stress condition direct flow (% ejection within the next heart beat) increased from 43 ± 6% to 53 ± 8%. 4D MRI blood flow acquisition and analysis are feasible in pig hearts under dobutamine‐induced stress. Flow patterns characterized by high blood velocity and antero‐septally oriented diastolic inflow as well as decreased ventricular volumes are unfavourable conditions for diastolic vortex development under pharmacological stress, and cardiac output is increased by a rise in heart rate and directly ejected left ventricular blood volume. In this study the feasibility of 4D flow MRI during dobutamine‐induced stress was assessed, and changes in intraventricular blood flow patterns are reported for the porcine heart. A decrease in cardiac volume, antero‐septally oriented diastolic inflow and high velocity flow was found, providing unfavorable conditions for diastolic vortex development compared with the rest condition. [ABSTRACT FROM AUTHOR]

During cardiac surgery local hypothermia of the heart is used to slow down cellular metabolism. It has been shown by computer simulation that heart muscle is not uniformly cooled to the desired temperatures. The aim of our work was to find out a way for measuring the temperatures of the ventricular wall and the septum with ± 0.1^C accuracy. The measurement protocol should be applicable during operations on the human heart, during which disturbing factors should be minimized. We have tested the protocol and the equipment on porcine hearts. Two types of probes were tested, the contact-probe, which can be attached to the heart-wall surface, and the needle-probe, which can be inserted into the heart tissue. Before experiments the probes were calibrated and their heat transfer characteristics determined. We conclude that the probes and the protocol are suitable for studying the effects of cardioplegia, and for checking the results previously obtained by computer simulation. [ABSTRACT FROM AUTHOR]

During cardiac surgery local hypothermia of the heart is used to slow down cellular metabolism. It has been shown by computer simulation that heart muscle is not uniformly cooled to the desired temperatures. The aim of our work was to find out a way for measuring the temperatures of the ventricular wall and the septum with ± 0.1^C accuracy. The measurement protocol should be applicable during operations on the human heart, during which disturbing factors should be minimized. We have tested the protocol and the equipment on porcine hearts. Two types of probes were tested, the contact-probe, which can be attached to the heart-wall surface, and the needle-probe, which can be inserted into the heart tissue. Before experiments the probes were calibrated and their heat transfer characteristics determined. We conclude that the probes and the protocol are suitable for studying the effects of cardioplegia, and for checking the results previously obtained by computer simulation.