n-3 Fatty acids, cardiac arrhythmia and fatal coronary heart disease

n-3 Polyunsaturated fatty acids (n-3 PUFA) are suggested to prevent cardiac death via inhibition of cardiac arrhythmia. In this review we discuss the results of human studies on intake of n-3 PUFAs and heart disease and, more specifically, on cardiac arrhythmia. Observational studies indicate that intake of fish is associated with a lower incidence of fatal coronary heart disease in several populations. These studies are fairly consistent, but people that have a high intake of fatty fish might have a healthier lifestyle in general, and such confounding is difficult to remove completely with statistical adjustments and corrections. Evidence from trials is less clear. In two open label trials in patients with a previous myocardial infarction intake of fish or fish oil prevented fatal coronary heart disease. In contrast, a trial in patients with angina suggested a higher risk of sudden cardiac death in patients taking fish oil. Furthermore, results of trials in patients with an implantable cardioverter defibrillator (ICD) that investigated effects of fish oil on arrhythmia in patients already suffering from ventricular tachycardia are not consistent. Also, studies on relationships between intake of n-3 PUFA from fish and less life-threatening forms of arrhythmia, such as atrial fibrillation and premature ventricular complexes (PVCs) are equivocal. Thus, after 35 years of research the question whether fish prevents heart disease remains unanswered, and an anti-arrhythmic effect of fish oil remains unproven although the idea is still viable and is being actively tested in further trials.     

Effect of temperature on heart rate in diploid and triploid brook charr, Salvelinus fontinalis, embryos and larvae

Increased cell size in triploid fish likely affects rates of respiratory gas exchange. Respiratory deficiencies can be addressed in fish by adjustments in cardiac output, through changes in heart rate and stroke volume. The aim of this study was to determine whether heart rate differs between triploid and control (diploid) brook charr, Salvelinus fontinalis, at embryo-larval stages, when the heart is easily visible and the fish are relatively inactive. Heart rate was measured at 6, 9 and 12 degrees C at three developmental stages: eyed-egg, hatch and yolk absorption. Heart rate was unaffected by ploidy, but increased with temperature and age from a low of 43.4+/-2.2 beats/min (6 degrees C, eyed egg) to a high of 73.3+/-1.5 beats/min (12 degrees C, yolk absorption). The Q(10) for heart rate was unaffected by ploidy and age, but decreased with temperature from 1.99+/-0.28 at 6-9 degrees C to 1.72+/-0.17 at 9-12 degrees C. Triploid brook charr thus do not use adjustments in heart rate as a mechanism to deal with the physiological consequences of altered haematology at embryo-larval stages.     

The cellular basis for enhanced volume-modulated cardiac output in fish hearts

During vertebrate evolution there has been a shift in the way in which the heart varies cardiac output (the product of heart rate and stroke volume). While mammals, birds, and amphibians increase cardiac output through large increases in heart rate and only modest increases (approximately 30%) in stroke volume, fish and some reptiles use modest increases in heart rate and very large increases in stroke volume (up to 300%). The cellular mechanisms underlying these fundamentally different approaches to cardiac output modulation are unknown. We hypothesized that the divergence between volume modulation and frequency modulation lies in the response of different vertebrate myocardium to stretch. We tested this by progressively stretching individual cardiac myocytes from the fish heart while measuring sarcomere length (SL), developed tension, and intracellular Ca2+ ([Ca2+]i) transients. We show that in fish cardiac myocytes, active tension increases at SLs greater than those previously demonstrated for intact mammalian myocytes, representing a twofold increase in the functional ascending limb of the length-tension relationship. The mechanism of action is a length-dependent increase in myofilament Ca2+ sensitivity, rather than changes in the [Ca2+]i transient or actin filament length in the fish cell. The capacity for greater sarcomere extension in fish myocardium may be linked to the low resting tension that is developed during stretch. These adaptations allow the fish heart to volume modulate and thus underpin the fundamental difference between the way fish and higher vertebrates vary cardiac output.     

Behavioural and heart rate responses to food limitation and predation risk: an experimental study on rainbow trout

Food-restricted rainbow trout Oncorhynchus mykiss maintained a lower basal heart rate than satiated fish, probably as a result of reduced metabolic rate. Food-restricted fish were also more active during feeding and were more willing to take risks than satiated fish. Both satiated and food-restricted fish were positioned lower in the tank after the predator attack. Heart rate increased more during feeding in the food-restricted fish compared to the satiated, but energy status had no general effect on the relation between heart rate and behaviour. Hence, the increase in heart rate was mainly a response to the more active foraging behaviour in the food-restricted fish. Moreover, behavioural activity in the food-restricted fish was associated with a higher heart rate after the predator attack than when the fish was undisturbed, which may reflect physiological preparation for flight. These findings suggest that behavioural and cardiac responses are coadapted to meet variation in food availability and predation risk in the wild.     

Fish oil and neurovascular control in humans

The antihypertensive influence of fish oil is controversial, and the mechanisms remain unclear. Because the inverse relation between fish oil and hypertension appears to be partially dependent on the degree of hypertension, we tested the hypothesis that fish oil would elicit more dramatic reductions in mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) in prehypertensive (PHT) compared with normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9 g/day; 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid) or placebo (olive oil; 9 g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (80 ± 1 to 80 ± 1 mmHg; 11 ± 2 to 10 ± 1 bursts/min; 71 ± 2 to 71 ± 2 beats/min) or PHT (88 ± 2 to 87 ± 1 mmHg; 11 ± 2 to 10 ± 2 bursts/min; 73 ± 2 to 73 ± 2 beats/min) subjects. When NT and PHT groups were consolidated, analysis of covariance confirmed that pretreatment resting MAP was not associated with changes in MSNA after fish oil. In contrast, pretreatment resting HR was correlated with changes in MSNA (r = 0.47; P = 0.007) and MAP (r = 0.42; P < 0.007) after fish oil but not placebo. In conclusion, fish oil did not alter sympathetic neural control in NT or PHT subjects. However, our findings suggest that fish oil is associated with modest sympathoinhibition in individuals with higher resting heart rates, a finding that is consistent with a recent meta-analysis examining the relations among fish oil, HR, and the risk of cardiovascular disease.     

Comparative studies on heart and skeletal muscle AMP-deaminase from rainbow trout (Salmo gairdneri).

1. AMP-deaminases from fish heart and skeletal muscle have been isolated, and their kinetic and regulatory properties compared. 2. The results obtained indicate that the enzyme variants present in fish heart and skeletal muscle, in contrast to their mammalian counterparts, show very similar chromatographic, kinetic and regulatory characteristics. 3. The above may reflect evolutionary programmed differences in AMP-deaminase gene(s) organization.     

The anatomical components of the cardiac outflow tract of chondrichthyans and actinopterygians

The outflow tract of the fish heart is the segment interposed between the ventricle and the ventral aorta. It holds the valves that prevent blood backflow from the gill vasculature to the ventricle. The anatomical composition, histological structure and evolutionary changes in the fish cardiac outflow tract have been under discussion for nearly two centuries and are still subject to debate. This paper offers a brief historical review of the main conceptions about the cardiac outflow tract components of chondrichthyans (cartilaginous fish) and actinopterygians (ray‐finned fish) which have been put forward since the beginning of the nineteenth century up to the current day. We focus on the evolutionary origin of the outflow tract components and the changes to which they have been subject in the major extant groups of chondrichthyans and actinopterygians. In addition, an attempt is made to infer the primitive anatomical design of the heart of the gnathostomes (jawed vertebrates). Finally, several areas of further investigation are suggested. Recent work on fish heart morphology has shown that the cardiac outflow tract of chondrichthyans does not consist exclusively of the myocardial conus arteriosus as classically thought. A conus arteriosus and a bulbus arteriosus, devoid of myocardium and mainly composed of elastin and smooth muscle, are usually present in cartilaginous and ray‐finned fish. This is consistent with the suggestion that both components coexisted from the onset of the gnathostome radiation. There is evidence that the conus arteriosus appeared in the agnathans. By contrast, the evolutionary origin of the bulbus is still unclear. It is almost certain that in all fish, both the conus and bulbus develop from the embryonic second heart field. We suggest herein that the primitive anatomical heart of the jawed vertebrates consisted of a sinus venosus containing the pacemaker tissue, an atrium possessing trabeculated myocardium, an atrioventricular region with compact myocardium which supported the atrioventricular valves, a ventricle composed of mixed myocardium, and an outflow tract consisting of a conus arteriosus, with compact myocardium in its wall and valves at its luminal side, and a non‐myocardial bulbus arteriosus that connected the conus with the ventral aorta. Chondrichthyans have retained this basic anatomical design of the heart. In actinopterygians, the heart has been subject to notable changes during evolution. Among them, the following two should be highlighted: (i) a decrease in size of the conus in combination with a remarkable development of the bulbus, especially in teleosts; and (ii) loss of the myocardial compact layer of the ventricle in many teleost species.     

Does respiratory sinus arrhythmia occur in fishes?

The hypothesis that respiratory modulation of heart rate variability (HRV) or respiratory sinus arrhythmia (RSA) is restricted to mammals was tested on four Antarctic and four sub-Antarctic species of fish, that shared close genotypic or ecotypic similarities but, due to their different environmental temperatures, faced vastly different selection pressures related to oxygen supply. The intrinsic heart rate (fH) for all the fish species studied was approximately 25% greater than respiration rate (fV), but vagal activity successively delayed heart beats, producing a resting fH that was synchronized with fV in a progressive manner. Power spectral statistics showed that these episodes of relative bradycardia occurred in a cyclical manner every 2-4 heart beats in temperate species but at >4 heart beats in Antarctic species, indicating a more relaxed selection pressure for cardio-respiratory coupling. This evidence that vagally mediated control of fH operates around the ventilatory cycle in fish demonstrates that influences similar to those controlling RSA in mammals operate in non-mammalian vertebrates.     

The effect of consuming different proportions of hummer fish on biochemical and histopathological changes of hyperglycemic rats

Hammour fish (grouper fish) are known to be of great nutritional value for human consumption, as their protein has a high biological value and contains all the essential amino acids. Grouper fish are also a good source of minerals, vitamins, and fats that contain essential fatty acids. Thus, the current study aims to know the effect of different proportion of hummer fish on biochemical and histopathological changes of hyperglycemic rats. Twenty-four (24) Sprague Dawley-strain male albino rats, which weighed 150 ± 10 g, were divided into four groups. One group served as the negative control (normal), while the others were rendered diabetic using alloxan. One of the diabetic groups was considered the positive control and fed a standard diet, whereas the remaining two groups were fed with a 20% and 25% hammour fish diet for 28 days. At the end of the experiment, blood samples were taken from all the rats, and their organs were removed and subjected to biochemical analysis. The results indicated that the group fed with the 25% hammour fish diet exhibited significantly lower levels of liver, kidney, and heart damage, along with lower levels of serum glucose, total cholesterol, triglycerides, LDL, GOT, GPT and ALP, as compared to the positive control. The urea and creatinine levels were significantly higher for the rats that were fed the 20% hammour fish diet than for those in the positive control. The histopathological study of the heart showed a slight improvement of the heart tissues with the increase of hammour fish intake compare to the positive control, while kidney of rat from group 4, which were fed 25% hammour fish, showed granularity of epithelial lining glomerular tufts.     

Effects of cadmium toxicity upon the in vivo and in vitro activity of proteins and five enzymes in blood serum and tissue homogenates of Mugil cephalus

This study reports changes in total protein and certain liver, heart, gill and serum enzymes after exposing fish or tissue homogenates and serum to Cd, i.e. in vivo and in vitro effects. Five enzymes were selected for assay; aspartate amino transferase (AAT), alanine amino transferase (A1AT), alkaline phosphatase (A1P), acid phosphatase (ACP) and lactic dehydrogenase (LDH). Total protein content in the exposed fish showed an increase in the liver, gill and serum while there was no change in heart protein. The sensitivity of the five assayed enzymes to Cd varied in different tissues. Gill AAT, A1AT were the most sensitive. Liver A1P and heart LDH showed the maximum inhibition at higher Cd concentrations.     

Angling-induced cardiac disturbance of free-swimming largemouth bass (Micropterus salmoides) monitored with heart rate telemetry

The sub‐lethal effects of catch‐and‐release angling have been poorly studied because of the difficulties in monitoring physiological parameters in free‐swimming fish. Laboratory studies provide the opportunity to examine sub‐lethal effects in controlled environments, but do not incorporate site‐specific characteristics. In this study we angled free‐swimming largemouth bass (Micropterus salmoides) equipped with heart rate transmitters to exhaustion using rod and reel, and exposed fish to air for 30 s. Experiments were repeated at four water temperatures (13, 17, 21, and 25°C). These field data were compared with published findings from largemouth bass collected at the same water temperatures in a controlled laboratory setting using Doppler flow probes. Field collected heart rate data increased with increasing water temperatures (Q₁₀ values 1.30–1.37). Pre‐disturbance heart rates were ～30% higher for free‐swimming fish in the field than previously collected laboratory data at the same water temperatures. Fish angled in the field exhausted ～40% more rapidly than fish chased in the laboratory. Maximal heart rate was ～15% higher for free‐swimming fish in the field than for data collected from laboratory restrained fish, but scope for heart rate was reduced by up to 20% in the field, especially at higher water temperatures. Heart rate in free‐swimming fish was highly variable at all times, obscuring clear recovery patterns. Conversely, laboratory cardiac parameters exhibited less variable patterns, peaking clearly following disturbances and recovering in about 135 min, independent of water temperature. Based upon these findings, we suggest that comprehensive studies incorporating both laboratory and field experiments are needed for truly understanding the effect of catch‐and‐release angling on fish.     

Comparative biochemical analysis of blood serum lipoproteins from human and various animal species

Lipid composition of blood serum and total lipids of low density lipoproteins (LDL) and high density lipoproteins (HDL2 and HDL3) were studied in human (donors, patients with ischemic heart disease, bronchial asthma, chronic obstructive bronchitis, as well as with a combined pathology), in mammals predisposed to atherosclerosis (pig, rabbit) and resistant to atherosclerosis (rat, mink, Arctic fox), in birds (hen, pigeon), in teleost fish (white fish, pikeperch, pike, bream, burbot) and cartilaginous fish (sturgeon, housen). It has been established that the most enriched in lipids is the blood serum of animals, particularly of cartilaginous fish. Twice lower is the lipid content in blood serum of donors than of animals. However, in the vascular, bronchial-pulmonary, and combined human pathologies the lipid level rises statistically significantly. In human and in animals predisposed to atherosclerosis the main mass of lipid is located in LDL, whereas in animals resistant to this disease--in HDL. The ratio of the human lipid content in LDL/HDL increases from 1.4 (in donors) to 2.7 in pathological states--in ischemic heart disease and its combination with chronic obstructive disease. In animals, a decrease of this ratio is noted from 1.0 to 0.2 in cartilaginous fish. By the example of one taxon (fish) there is established a regularity that indicates that evolution of lipoproteins occurred with an increase of the lipid amount in the "younger" LDL and with a decrease of concentration of the "colder" HDL.     

Phenotypic plasticity and predator effects on morphology and physiology of crucian carp in nature and in the laboratory

Crucian carp Carassius carassius show great phenotypic plasticity in individual morphology and physiology, and strong variation in population density in different fish communities. Small fish with shallow bodies and large heads are typical in overcrowded monospecific fish communities in small ponds, whereas deep-bodied, large fish are found in larger, multispecies lakes. Crucian carp are especially vulnerable to predation by piscivorous fish and their greater relative body depth in multispecies fish communities has been proposed to be an induced defence against size-limited predation, and hence to be an adaptive feature. Data are presented here on the two divergent body forms in field populations in eastern Finland, together with results of laboratory experiments on predator effects on morphology and physiology (growth, respiration, heart rate). The deep body can be achieved in a few months by introducing a low population density of shallow-bodied fish into a food-rich environment with no piscivores. In the laboratory, both the presence of piscivores (chemical cues) and enhanced food availability increased the relative depth of crucian carp, but only to a modest extent when compared to natural variation. It is concluded that the deep-body form of crucian carp in the low density populations of multispecies fish communities is the normal condition. Reproduction in monospecific ponds results in high intraspecific competition, low growth rate and a stunted morphology. According to pilot tests, the mechanism behind the predator effect in the laboratory might be a behavioural reaction to chemical cues (alarm substances/predator odour) causing changes in energy allocation: predator-exposed crucian carp adopt a 'hiding' mode with decreased activity (less swimming, lower respiration and heart rate) and with higher overall growth. Whether, and to what extent, this predator-induced mechanism works in nature is unclear.     

Comparative-biochemical analysis of lipids of blood serum lipoproteins of human and some animal species

Lipid composition of blood serum and total lipids of low density lipoproteins (LDL) and high density lipoproteins (HDL₂ and HDL₃) were studied in human (donors, patients with ischemic heart disease, bronchial asthma, chronic obstructive bronchitis, as well as with a combined pathology), in mammals predisposed to atherosclerosis (pig, rabbit) and resistant to atherosclerosis (rat, mink, Arctic fox), in birds (hen, pigeon), in teleost fish (white fish, pike-perch, pike, bream, burbot) and cartilaginous fish (sturgeon, housen). It has been established that the most enriched in lipids is the blood serum of animals, particularly of cartilaginous fish. Twice lower is the lipid content in blood serum of donors than of animals. However, in the vascular, bronchopulmonary, and combined human pathologies the lipid level rises statistically significantly. In human and in animals predisposed to atherosclerosis the main mass of lipid is located in LDL, whereas in animals resistant to this disease—in HDL. The ratio of the human lipid content in LDL/HDL increases from 1.4 (in donors) to 2.7 in pathological states—in ischemic heart disease and its combination with chronic obstructive disease. In animals, a decrease of this ratio is noted from 1.0 to 0.2 in cartilaginous fish. By the example of one taxon (fish) there is established a regularity that indicates that evolution of lipoproteins occurred with an increase of the lipid amount in the “younger” LDL and with a decrease of concentration of the “older” HDL.     

Features heightening cardiovascular performance in fishes,with special reference to tunas

Information on heart rate, cardiac mass, vascular resistance, and myocardial oxygen consumption are considered with a view to identifying special features that heighten cardiovascular performance in fish, and especially in tuna. Fish rarely have heart rates greater than 120 bpm. Skipjack tuna are an exception, with heart rates approaching those of similarly sized mammals. A large relative ventricular mass is a characteristic of, but not exclusive to, active fish. However, the pyramidal shape of this large ventricle in active fish is a distinguishing characteristic. This anatomical form may be important in the coupling of high cardiac stroke volumes (around 1 mL/kg) with high heart rates and blood pressures. Skipjack tuna excel in this regard. The characteristically high cardiac power output and large ventricular mass in active fish necessitates a coronary circulation. In most active fish, however, the coronary circulation is important under extreme conditions (e.g., swimming and hypoxia) rather than for routine performance. Skipjack tuna may be an exception, requiring their coronary circulation for routine performance. Neither total vascular resistance nor the relative O₂ cost of cardiac pumping stand out as being unusual in active fish. Even so, the unusually high resistance of the branchial circulation in skipjack tuna may represent an upper design limit for the structure of individual lamellae.     

Cardiac conduction times in Sparus auratus at different heart rates. Influence of body weight

At different heart rates, the conduction time through the atrium of gilthead sea bream Sparus auratus (P-R interval) was constant in each fish but differed from one fish to another. This difference was not related to the body size of the animal, suggesting the lack of preferential conduction pathways in the atrium. A clear relation between R-T interval and fish weight was observed, suggesting a similar conduction speed of the excitatory wave and the presence of specialized conductive tissue in the ventricle. Moreover, the P-R and R-T intervals did not participate in the determination of the heart rate, and all changes in the heart rate were related to changes in the T-P interval.     

3D heart morphological changes in response to developmental temperature in zebrafish: More than ventricle roundness

A new, three‐dimensional geometric morphometric approach was assessed to study the effect of developmental temperature on fish heart shape utilizing geometric morphometrics of three‐dimensional landmarks captured on digitally reconstructed zebrafish hearts. This study reports the first three‐dimensional analysis of the fish heart and demonstrates significant shape modifications occurring after three developmental temperature treatments (T_D = 24, 28 or 32°C) at two distinct developmental stages (juvenile and adult fish). Elevation of T_D induced ventricle roundness in juveniles, males and females. Furthermore, significant differences that have not been described so far in heart morphometric indices (i.e., ventricle sphericity, bulbus arteriosus elongation and relative location, heart asymmetry) were identified. Sex proved to be a significant regulating factor of heart shape plasticity in response to T_D. This methodology offers unique benefits by providing a more precise representation of heart shape changes in response to developmental temperature that are otherwise not discernable with the previously described two‐dimensional methods. Our work provides the first evidence of three‐dimensional shape alterations of the zebrafish heart adding to the emerging rationale of temperature‐driven plastic responses of global warming and seasonal temperature disturbances in wild fish populations and in other ectothermic vertebrates as well (amphibians and reptiles).     

Functional Morphology of the Heart in Fishes

The systemic heart of fishes consists of four chambers in series,the sinus venosus, atrium, ventricle, and conus or bulbus. Valvesbetween the chambers and contraction of all chambers exceptthe bulbus maintain a unidirectional blood flow through theheart. The heart is composed of typical vertebrate cardiac muscle,although there may be minor differences in the distributionof spontaneously active cells, the rate and nature of spreadof excitatory waves, and the characteristics of resting andaction potentials between different fish and other vertebrates.Cholinergic fibers innervate the heart, except in hagfish whichhave aneural hearts. Fish hearts lack sympathetic innervation.The level of vagal tone varies considerably, and is affectedby many factors. In some fish the heart is essentially aneural(without vagal tone) during exercise and may resemble an isolatedmammalian ventricle with increased venous return causing increasedcardiac output. There are many mechanisms that could increasevenous return in exercising fish. rß-adrenergic receptorshave been located on the hearts of some fish, and changing levelsof catecholamines may play a role in regulating cardiac activity.Changes in cardiac output in fish are normally associated withlarge changes in stroke volume and small cha-nges in heart rate.     

Fatty acid composition of choline and ethanolamine glycerophospholipid subclasses in heart tissue of mammals and migratory and demersal fish

The distribution and fatty acid composition of cardiac choline and ethanolamine glycerophospholipids in both migratory and demersal fish and bovine and pig were determined. Phospholipid contents (mg/g heart) were 4.7-9.4 in demersal fish, 14.0-16.5 in migratory fish, and 16.8-20.6 in mammals. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were the major components in the phospholipid fraction. Diacyl forms represented 50.2-88.1% of PC in all animals, while plasmalogens comprised 47.0% in bovine, 8.2% in pig and 6.2-7.2% in four species of fish. In PE, plasmalogens varied from 45.0% in bovine and 57.9% in pig to 26.1-29.7% in fish. This glycerophospholipid subclass was identified as containing higher proportions of polyunsaturated fatty acids (PUFAs; 20:4, 20:5, and 22:6) than found in alkylacyl- and diacyl-glycerophospholipids. Qualitative and quantitative differences were found in PE-plasmalogen between land mammals and fish, especially with regard to n-3 fatty acid composition, but no significant difference was noted between migratory and demersal fish.